Background:Cucurbita maxima plant materials are frequently used to manage a number of disorders,according to previous studies.Objective:The goal of the present report was to look into further possible effects of this ...Background:Cucurbita maxima plant materials are frequently used to manage a number of disorders,according to previous studies.Objective:The goal of the present report was to look into further possible effects of this plant on kidney disorder in rats brought on by diabetes as well as the related abnormalities in lipid metabolism.Methods:To assess the ameliorative effect of the plant,streptozotocin(STZ)(45 mg/kg/day)was given as a single dosage to cause type 1 diabetes.After then,diabetic rats received supplemented diets of Cucurbita maxima for four weeks at 5%,10%,15%and 20%ad libidium.However,in another experiment to evaluate the preventive capacity of Cucurbita maxima,the STZ-induction came at the end of four weeks supplementation.Blood and kidney tissues were obtained at the end of the treatments and investigated.Consequently,the analysis of kidney function and lipid profile was made using serum obtained from the blood sample.Histological change in kidney was also observed using haematoxylin and eosin stain Results:Our findings demonstrated that Cucurbita maxima drastically(P<0.05)decreased the elevated kidney indicators such as urea and creatinine in the blood,and restored the electrolytes and lipid profiles anomalies as compared to the normal control.However,the alteration of biochemical parameters in the STZ-induced diabetic control remained unchanged throughout as compared to the normal control.The above mentioned biochemical changes that took place in kidney tissues were further corroborated by histological alterations.Conclusion:The results suggest that Cucurbita maxima leaves supplemented diets reversed STZ-induced renal disorder and abnormal lipid metabolism,and that these effects may be mediated by interacting with multiple receptors to raise the levels of antioxidant enzymes in the system.展开更多
Research Background and Purpose: The number of diabetic patients is rapidly increasing, making it crucial to find methods to prevent diabetic retinopathy (DR), a leading cause of blindness. We investigated the effects...Research Background and Purpose: The number of diabetic patients is rapidly increasing, making it crucial to find methods to prevent diabetic retinopathy (DR), a leading cause of blindness. We investigated the effects of prophylactic pattern scanning laser retinal photocoagulation on DR development in Spontaneously Diabetic Torii (SDT) fatty rats as a new prevention approach. Methods: Photocoagulation was applied to the right eyes of 8-week-old Spontaneously Diabetic Torii (SDT) fatty rats, with the left eyes serving as untreated controls. Electroretinography at 9 and 39 weeks of age and pathological examinations, including immunohistochemistry for vascular endothelial growth factor and glial fibrillary acidic protein at 24 and 40 weeks of age, were performed on both eyes. Results: There were no significant differences in amplitude and prolongation of the OP waves between the right and left eyes in SDT fatty rats at 39 weeks of age. Similarly, no significant differences in pathology and immunohistochemistry were observed between the right and left eyes in SDT fatty rats at 24 and 40 weeks of age. Conclusion: Prophylactic pattern scanning retinal laser photocoagulation did not affect the development of diabetic retinopathy in SDT fatty rats.展开更多
AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl trans...AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.展开更多
Objective To screen and identify differentially expressed genes in the dorsal root ganglion （DRG） in early experimental diabetic rats. Methods Diabetic model rats were induced by single intraperitoneal injection of ...Objective To screen and identify differentially expressed genes in the dorsal root ganglion （DRG） in early experimental diabetic rats. Methods Diabetic model rats were induced by single intraperitoneal injection of streptozotocin （STZ）. At the second week after STZ injection, the sensory nerve conduction velocities （SNCV） of sciatic nerve were measured as an indicator of neuropathy. The technique of silver-staining mRNA differential display polymerase chain reaction （DD-PCR） was used to detect the levels of differentially expressed genes in rat DRG. The cDNA fragments that displayed differentially were identified by reverse-hybridization, cloned and sequenced subsequently, and then confirmed by Northern blot. Results The SNCV in the diabetic model group [n = 9, （45.25±10.38） m/s] reduced obviously compared with the control group [n = 8, （60.10± 11.92） m/s] （P 〈 0.05）. Seven distinct cDNA clones, one was up-regulated gene and the others were downregulated ones, were isolated by silver-staining mRNA differential display method and confirmed by Northern blot. According to the results of sequence alignment with GenBank data, majority of the clones had no significant sequence similarity to previously reported genes except only one that showed high homology to 6-pyruvoyl-tetrahydropterin synthase mRNA （accession No., BC059140）, which had not been reported to relate to diabetic neuropathy. Conclusion These differentially expressed genes in the diabetic DRG may contribute to the pathogenesis of diabetic peripheral neuropathy.展开更多
Objective To investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin （EM） on the regulation of gastric motility in diabetic rats. Met...Objective To investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin （EM） on the regulation of gastric motility in diabetic rats. Methods The motilin immunoreactive neurons in the hypothalamus and the hippocampus were detected by immunohistochemistry with rabbit anti-motilin polyclonal antibody. To measure the gastric motility, force transducers were surgically affixed to the gastric serosa. A microinjection syringe was connected via a plastic tube to an injection cannula, which was connected with a stainless steel guide cannula. The syringe was inserted into the right lateral cerebral ventricle for microinjecting the chemicals. Results Diabetic mellitus was successfully induced in cohorts of rats. Motilin-immunoreactive neurons significantly increased in the paraventricular （PVN） and supraoptic nuclei （SON） of the hypothalamus in the diabetic rats. Intracerebroventricular （i.c.v.） administration of EM, a motilin receptor agonist, stimulated the gastric motility of diabetic rats. EM （91.56 nmol, i.c.v.） dose-dependently increased the amplitude by （174.82±48.62）% （P 〈 0.05）, and increased the frequency by （70.43±27.11）% （P 〈 0.05） in 5 min. The stimulatory effect lasted more than 15 min to the end of the measurement, and can be blocked partially by the prior treatment of motilin receptor antagonist GM-109. Conclusion Motilin-immunoreactive neurons are increased in the PVN and SON of the hypothalamus in diabetic rats. Centrally administered EM may regulate gastric motility by binding to the central motilin receptors, and central motilin might be involved in regulation of gastric motility in diabetic rats.展开更多
Objective To investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats. Methods Thirty Sprague-dawley female rats were randomly divided into three groups （n=10 e...Objective To investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats. Methods Thirty Sprague-dawley female rats were randomly divided into three groups （n=10 each）, ＂control group＂ with intraperitoneal saline injection, ＂diabetic group＂ with 60 mg of intraperitoneal streptozotocin injection per kg of body weight and ＂Hsian-tsao group＂ with intragastric administration of Hsian-tsao extraction everyday for 4 weeks after intraperitoneal streptozotocin injection. The body weight and blood sugar were measured before and after model induction in the three groups. Thrombospondin-1 （TSP-1） expressions in the kidney were monitored by immunohistochemistry. Kidney ultrastructural changes were also analyzed by using transmission electron microscopy. Results Before diabetic model induction, there were no significant differences among the three groups in body weight and blood sugar. Four weeks after the induction of diabetes, the differences became statistically significant. Electron microscopy also revealed disruption of the foot processes of the podocytes and other damages in diabetic group. These damages were significantly less severe in Hsian-tsao group when compared with the diabetic group. TSP-1 expressions in the kidney were significantly increased in both the diabetic group and Hsian-tsao group, but it was relatively lower in Hsian-tsao group than in diabetic group. Conclusion Our results showed that Hsian-tsao treatment in the diabetic rats effectively prevented the pathological alterations in the kidney and decreased the TSP- 1 expression. It was suggested that Hsian-tsao had protective effect on the kidneys of the diabetic rats.展开更多
Objective:To investigate the antidiabetic properties of aqueous extract of stem bark of Afzelia africana(A.africana)and its beneficial effect on haematological parameters in streptozotocin induced diabetic rats.Method...Objective:To investigate the antidiabetic properties of aqueous extract of stem bark of Afzelia africana(A.africana)and its beneficial effect on haematological parameters in streptozotocin induced diabetic rats.Methods:A total of 30 rats including 24 diabetic and 6 normal rats were used for this study.Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin.After being confirmed diabetic,animals were orally treated with distilled water or extracts at 100 or 200 mg/kg body weight daily for 10 days.The haematological parameters including red blood and white blood cells and their functional indices were evaluated in diabetic treated groups compared with the controls.Results:The extract significantly reduced the blood glucose levels while the best result was obtained at 200 mg/kg body weight The feed and water intake in diabetic rats were significantly reduced while weight loss was minimized at both dosages.Similarly,the levels of red blood,white blood cells and their functional indices were significantly improved after extract administration at both doses.Conclusions:It can be concluded that the aqueous extract of bark of A.africana possesses antihyperglycemic properties.In addition,the extract can prevent various complications of diabetes and improve some haematological parameters.Further experimental investigation is needed to exploit its relevant therapeutic effect to substantiate its ethnomedicinal usage.展开更多
Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was indu...Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was induced by a single administration of streptozotocin(50 mg/kg)and the rats were treated for 7 weeks.Antioxidant enzymes[calalase(CAT),glutathione peroxidase(GPx),superoxide dismutase(SOD)],antioxidant capacity[trolox equivalence antioxidant capacity(TEAC),oxygen radical absorbance capacity(ORAC)]as well as total protein,albumin,globulin,total glutathione,conjugated diene and thiobarbituric acid reactive substances(TBARS)were investigated.Results:Treatment with RPO,RTE and RPO+RTE significantly(p>0.05)improved liver SOD and plasma ORAC in the diabetic rats.Similarly,diabetic rats treated with RTE and RPO+RTE enhanced liver GPx.A significant(P<0.05)increase in the plasma TBARS in the diabetic control group was observed when compared with the normal control group.Treatment of diabetic rats with RTE and RPO+RTE reduced plasma TBARS to a level not significantly different at P<0.05 from the normal control group.Conclusions:The results revealed the anti-oxidative potentials of red palm oil,rooibos and their combination in diabetic conditions and hence,they could be useful in the management of diabetes and its complications.展开更多
Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats...Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P<0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P<0.07)but reduced glutathione content was found to be increased significantly(P<0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.展开更多
AIM: To evaluate the effects of etanercept on the expression of Fas, tumor necrosis factor-alpha(TNF-α) and caspase-8 in the early stage of the apoptotic pathway in diabetic rats, and to explore the therapeutic effec...AIM: To evaluate the effects of etanercept on the expression of Fas, tumor necrosis factor-alpha(TNF-α) and caspase-8 in the early stage of the apoptotic pathway in diabetic rats, and to explore the therapeutic effect of etanercept on diabetic retinopathy.METHODS: A total of 60 Sprague-Dawley(SD) rats were randomly and evenly divided into 3 groups with 20 rats each, including control group, and diabetic groups with or without treatment. Streptozotocin(STZ)-induced diabetic rats were established for diabetic groups. Blood glucose and body weight were measured weekly. All the rats were sacrificed at the 12 wk after treatment. The expressions of Fas, TNF-α and caspase-8 in rat retina were quantitatively detected by PCR and Western blot. The leakage of Evan blue was adopted to measure the retinal vascular leakage quantitatively, and to compare it among different groups. TUNEL method was used to compare the amount of apoptotic bodies quantitatively in rat retina ganglion cells under electron microscope.RESULTS: The expressions of Fas, TNF-α and caspase-8 in each group were compared via PCR and Western blot, in which the diabetic group with treatment was lower than those without treatment(P<0.01), but all the diabetic groups were higher than the control group(P<0.01). Evans blue leakage in the diabetic treatment group was lower than those without treatment(P<0.01), but those in the control group was the lowest compared with the other two groups(P<0.01). TUNEL method showed that the apoptoticbodies of retina in the diabetic treatment group was lower than those without treatment(P<0.01), while those in the control group was the lowest compared with the other two groups(P<0.01). CONCLUSION: Etanercept can effectively reduce the expression of Fas, TNF-α and caspase-8, as well as the retinal leakage and retinal cell apoptosis in diabetic rats.展开更多
An Otsuka Long-Evans Tokushima Fatty(OLETF)rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.We investigated the eff...An Otsuka Long-Evans Tokushima Fatty(OLETF)rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.We investigated the effects of sericin on corneal wound healing in OLETF rats.Corneal wounds were prepared by removal of the corneal epithelium and documented using a TRC-50X.Sericin was instilled into the eyes of rats five times a day following corneal abrasion.The plasma levels of glucose,triglycerides,cholesterol and insulin in 38 wk old OLETF rats were significantly higher than in normal control rats(LETO rats),and the rate of corneal wound healing in OLETF rats was slower than in normal rat,probably due to the suppression of cell migration and proliferation caused by high plasma glucose levels.The corneal wounds of OLETF rats instilled with saline showed almost complete healing 72h after corneal epithelial abrasion.On the other hand,the instillation of sericin has a potent effect in promoting wound healing and wound size reduction in OLETF rats and the wounds showed almost complete healing at 48 h after abrasion.The sericin may be an effective and safe drug to promote corneal wound healing in diabetic keratopathy.展开更多
AIM: To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type -2...AIM: To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type -2 diabetes, and then to investigate the mechanisms. METHODS: ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS: DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c 1094 (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION: DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism.展开更多
AIM： To investigate the effect of a Chinese medicine, Kaiyu Qingwei Jianji （KYQWJJ） used for diabetic treatment, on the morphometry and residual strain distribution of the small intestine in streptozotocin （STZ） ...AIM： To investigate the effect of a Chinese medicine, Kaiyu Qingwei Jianji （KYQWJJ） used for diabetic treatment, on the morphometry and residual strain distribution of the small intestine in streptozotocin （STZ） -induced diabetic rats. Correlation analysis was also performed between the opening angle and residual strain with the blood glucose level. METHODS： Forty-two male Wistar rats weighing 220-240 g were included in this study. Thirty-two STZ- induced diabetic rats were subdivided into four groups （n = 8 in each group）, i.e. diabetic control group （DM）; high dose of KYQWJJ （T1, 36g/kg per day）; low dose of KYQWJJ （T2, 17 g/kg per day） and Gliclazide （T3, 50 mg/kg per day）. Another ten rats were used as nondiabetic control （CON）. The medicines were poured directly into stomach lumen by gastric lavage twice daily. The rats of CON and DM groups were only poured the physiological saline. Blood glucose and plasma insulin levels were measured. Experimental period was 35 d. At the end of experiment, three 5-cm long segments were harvested from the duodenum, jejunum and ileum. Three rings of 1-2 mm in length for no-load and zero-stress state tests were cut from the middle of different segments. The morphometric data, such as the circumferential length, the wall thickness and the opening angle were measured from the digitized images of intestinal segments in the no-load state and zerostress state. The residual strain was computed from the morphometry data. Furthermore, the linear regression analysis was performed between blood glucose level with morphometric and biomechanical data in the different intestinal segments. RESULTS： The blood glucose level of DM group was consistent 4-fold to 5-fold higher than those in CON group during the experiment （16.89 ± 1.11 vs 3.44 ± 0.15 mmol/L, P 〈 0.001）. The blood glucose level in the T1 （16.89 ± 1.11 vs 11.08 ± 2.67 mmol/L, P 〈 0.01） and T3 groups （16.89 ± 1.11 vs 13.54 ± 1.73 mmol/L, P 〈 0.05）, but not in T2 group （P 〉 0.05） was significantly lower than those in DM group. The plasma insulin levels of DM, T1, T2 and T3 groups were significantly lower than those in CON group （10.98 ± 1.02, 12.52 ± 1.42,13.54 ± 1.56,10.96 ± 0.96 vs 17.84 ± 2.34 pmol/L respectively, P 〈 0.05）, but no significantly difference among the groups with exception of CON group. The wet weight/cm and total wall thickness of duodenum, jejunum and ileum in DM group were significantly higher than those in CON group （wet weight （g/cm）： duodenum 0.209 ± 0.012 vs 0.166 ± 0.010, jejunum 0.149 ± 0.008 vs 0.121 ± 0.004, ileum 0.134 ± 0.013 vs 0.112 ± 0.007; Wall thickness （mm）： duodenum 0.849 ± 0.027 vs 0.710 ± 0.026, jejunum 0.7259 ± 0.034 vs 0.627 ± 0.025, ileum 0.532 ± 0.023 vs 0.470 ± 0.010, all P 〈 0.05）, T1 and T3 treatment could partly restore change of wall thickness, but T2 could not. The opening angle and absolute value of inner and outer residual stain were significantly smaller in duodenal segment （188 ± 11 degrees, -0.31 ± 0.02 and 0.35 ± 0.03 vs 259 ± 15 degrees, -0.40 ± 0.02 and 0.43 ± 0.05） and larger in jejunal （215 ± 20 degrees, -0.30 ± 0.03 and 0.36 ± 0.06 vs 172 ± 19 degrees, -0.25 ± 0.02 and 0.27 ± 0.02） and ileal segments （183 ± 20 degrees, -0.28 ± 0.01 and 0.34 ± 0.05 vs 153 ± 14 degrees, -0.23 ± 0.03 and 0.29 ± 0.04） in DM group than in CON group （P 〈 0.01）. TI and T3 treatment could partly restore this biomechanical alteration, but strong effect was found in T1 treatment （duodenum 243 ± 14 degrees, -0.36 ± 0.02 and 0.42 ± 0.06, jejunum 180 ± 15 degrees, -0.26 ± 0.03 and 0.30 ± 0.06 and ileum 163 ± 17 degrees, -0.23 ± 0.03 and 0.30 ± 0.05, compared with DM, P 〈 0.05）. The linear association was found between the glucose level with most morphometric and biomechanical data. CONCLUSION： KYQWJJ （high dose） treatment could partly restore the changes of blood glucose level and the remodeling of morphometry and residual strain of small intestine in diabetic rats. The linear regression analysis demonstrated that the effect of KYQWJJ on intestinal opening angle and residual strain is partially through its effect on the blood glucose level.展开更多
AIM: To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. METHODS: Thirty-six male Wistar rats and 18 male Lewis rat...AIM: To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. METHODS: Thirty-six male Wistar rats and 18 male Lewis rats were used as recipients and donors respectively. Diabetes was induced by the use of streptozotocin (60 mg/kg) intraperitoneally. Unpurified islets were isolated using the collagenase digestion technique and transplanted into the splenic parenchyma. The recipients were randomly assigned to one of the following three groups: group A (control group) had no immunosuppression; group B received cyclosporine (CsA) (5 mg/kg); group C receivedmycophenolate mofetil (MMF) (20 mg/kg). The animalswere killed on the 12th d. Blood and grafted tissues were obtained for laboratory and histological assessment. RESULTS: Median allograft survival was significantly higher in the two therapy groups than that in the controls (10 and 12 d for CsA and MMF respectively vs 0 d for the control group, P＜0.01). No difference in allograft survival between the CsA and MMF groups was found. However,MMF had less renal and hepatic toxicity and allowed weight gain.CONCLUSION: Monotherapy with MMF for immunosu ppression was safe in an experimental model of islet allotransplantation and was equally effective with cyclosporine, with less toxicity.展开更多
AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced d...AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced diabetic SpragueDawley(SD) rat model.METHODS: SD rats were administered an abdominal injection of STZ and induced to a diabetic model. After 6 wk course of diabetes, the treatment groups were given β-elemene through periocular and intravitreous injection separately and the control groups were given blank emulsion injection. HE staining was used to observe the morphology of retina. The m RNA expressions of HIF-1α, VEGF and i NOS was assayed by real-time polymerase chain reaction(PCR) and the protein expression was measured by Western blot and immunocytochemistry methods.RESULTS: The results indicated that the protein and m RNA expressions of HIF-1α, VEGF and i NOS after treated by β-elemene periocularly and intravitreally injections were all found to be reduced compared with the levels in the diabetic rats group(P<0.05). The inhibitory effect of intravitreal injection was more remarkable.CONCLUSION: The results show β-elemene protect the retina of diabetic rats from high glucose damage by downregulating the expression of HIF-1α, VEGF and iNOS.展开更多
AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabet...AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.展开更多
AIM： To investigate the effect of Tangweian Jianji （TWAJJ） on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats. METHODS： Diabetes was induced in 27 rats by in- j...AIM： To investigate the effect of Tangweian Jianji （TWAJJ） on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats. METHODS： Diabetes was induced in 27 rats by in- jecting streptozotocin （40 mg/kg body weight）, the animals were then divided into three groups （n = 9 in each group）, i.e., diabetic control （DM）; high dose （10 g/kg, T1） and low dose （5 g/kg, T2）. Another 10 rats acted as normal controls （Control）. TWAJJ was admin- istered by gavage once daily. Blood glucose and serum insulin levels were measured. Circumferential length, wall thickness and opening angle were measured from esophageal, duodenal, jejunal and ileal ring segments. The residual strain was calculated from the morpho- metric data. Step-wise distension was carried out on esophageal and jejunal segments. The obtained data on the length, diameter and pressure changes were then used to calculate the circumferential and longitu- dinal stresses and strains. Real-time reverse transcrip- tion polymerase chain reaction was used to detect the receptor of advanced glycation end-products （RAGE） mRNA level in jejunal tissues. RESULTS： At the end of the experiment, the blood glucose level was significantly higher and the serum insulin level was significantly lower in DM, T1 and T2 groups than in the control group （Glucose： 30.23 ± 0.41 mmol/L, 27.48 ± 0.27 mmol/L and 27.84 ± 0.29 mmol/ L vs 5.05 ± 0.04 mmol/L, P = 1.65 x 10-16, P = 5.89 x 1019 and P = 1.63 x 10-Is, respectively; Insulin： 1.47 ± 0.32 °tg/L, 2.66 ± 0.44 pg/L, 2.03 ± 0.29 pg/L and 4.17 ± 0.54 pg/L, P = 0.0001, P = 0.029 and P = 0.025, re- spectively）. However, these levels did not differ among the DM, T1 and T2 groups. The wet weight per unit length, wall thickness and opening angle of esophageal and intestinal segments in the DM group were signifi- cantly higher than those in the control group （from P = 0.009 to P = 0.004）. These parameters in the T1 group were significantly lower than those in the DM group （wet weight, duodenum： 0.147 ± 0.003 g/cm vs 0.158 ± 0.001 g/cm, P = 0.047; jejunum, 0.127 ± 0.003 g/cm vs 0.151：1：0.002 g/cm, P = 0.017; ileum, 0.127 ± 0.004 g/cm vs 0.139 ± 0.003 g/cm, P = 0.046; wall thickness, esophagus： 0.84±0.03 mm vs 0.94 ± 0.02 ram, P = 0.014; duodenum： 1.27 ± 0.06 mm vs 1.39 ± 0.05 ram, P = 0.031; jejunum： 1.19 ± 0.07 mm vs 1.34 ± 0.04 mm, P = 0.047; ileum： 1.09 ± 0.04 mm vs 1.15 ± 0.03 mm, P = 0.049; opening angle, esophagus： 112.2 ± 13.2° vs 134.7 ± 14.7°, P = 0.027; duodenum： 105.9 ± 12.3° vs 123.1 ± 13.1°, P = 0.046; jejunum： 90.1 ± 15.4° vs 115.5 ± 13.3°, P = 0.044; ileum： 112.9 ± 13.4° vs 136.1 ± 17.1°, P = 0.035）. In the esophageal and jejunal segments, the inner residual stain was significantly smaller and the outer residual strain was larger in the DN group than in the control group （P = 0.022 and P = 0.035）. T1 treatment significantly restored this biomechanical alteration （P = 0.011 and P = 0.019）, but T2 treatment did not. Fur- thermore, the circumferential and longitudinal stiffness of the esophageal and jejunal wall increased in the DM group compared with those in the control group. T1, but not T2 treatment, significantly decreased the cir- cumferential wall stiffness in the jejunal segment （P = 0.012） and longitudinal wall stiffness in the esophageal segment （P = 0.023）. The mRNA level of RAGE was significantly decreased in the T1 group compared to that in the DN group （P = 0.0069）. CONCLUSION： TWAJJ （high dose） treatment partly restored the morphometric and biomechanical remodel- ing of the upper gastrointestinal tract in diabetic rats.展开更多
AIM:To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions.METHODS:Seven diabetic Goto-Kakizaki(GK)male rats,...AIM:To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions.METHODS:Seven diabetic Goto-Kakizaki(GK)male rats,32-wk old(GK group),and 9 age-matched normal Wistar rats(Normal group)were included in the study.Jejunal segments were distended up to a pressure of10 cm H2O in an organ bath containing 37℃Krebs solution with addition of carbachol(CA).The pressure and outer diameter changes were synchronously recorded.Passive conditions were obtained using calcium-free Krebs solution containing ethylene glycol tetraacetic acid and papaverine.Total phasic,tonic and passive circumferential stress and strain were computed from the diameter and pressure data with reference to the zero-stress state geometry.The active phasic and tonic stresses were defined as the total phasic and tonic stresses minus the passive stress.RESULTS:Diabetes increased jejunal mucosa and muscle layer thicknesses compared to the Normal group(mucosa,755.8±63.3 vs 633.1±59.1μm,P<0.01;muscle,106.3±12.9 vs 85.2±11.7μm,P<0.05).The pressure and stress thresholds were decreased in the GK group after CA application compared to distensions without CA application(pressure,1.01±0.07vs 1.99±0.19 cmH2O,P<0.01;stress,0.11±0.01vs 0.24±0.02 kPa,P<0.01).CA application did not change the pressure and stress threshold in the Normal group(pressure,2.13±0.32 vs 2.34±0.32 cm H2O,P>0.05;stress,0.25±0.03 vs 0.35±0.06 kPa,P>0.05).The amplitude of total phasic,total tonic,active phasic and active tonic circumferential stresses did not differ for the distensions without CA application between the GK group and the Normal group.However,the total phasic and total tonic stresses increased after CA application in the GK group compared those in the Normal group.When normalized to muscle layer thickness,the amplitude of active stresses before CA application was lowest in the GK group compared with the Normal group.No difference was found during CA application.CONCLUSION:The stress generated by intestinal muscle normalized to the muscle layer thickness was lowest in GK rats compared to normal rats whereas the response to CA stimulation was preserved.展开更多
Objective:To investigate the hypoglycemic effect of the aqueous extract of Octomeles sumatrana (O.sumatrana)(OS) in streptozotocin-induced diabetic rats(STZ) and its molecular mechanisms. Methods:Diabetes was induced ...Objective:To investigate the hypoglycemic effect of the aqueous extract of Octomeles sumatrana (O.sumatrana)(OS) in streptozotocin-induced diabetic rats(STZ) and its molecular mechanisms. Methods:Diabetes was induced by intraperitoneal(i.p.) injection of streptozotocin(55 mg/kg) in to male Sprague-Dawley rats.Rats were divided into six different groups;normal control rats were not induced with STZ and served as reference,STZ diabetic control rats were given normal saline.Three groups were treated with OS aqueous extract at 0.2,0.3 and 0.5 g/kg,orally twice daily continuously for 21 d.The fifth group was treated with glibenclamide(6 mg/kg) in aqueous solution orally continuously for 21 d.After completion of the treatment period,biochemical parameters and expression levels of glucose transporter 2(Slc2a2),glucose-6-phosphatase (GoPase) and phosphoenolpyruvate carboxykinase(PCK1) were determined in liver by quantitative real time PCR.Results:Administration of OS at different doses to STZ induced diabetic rats, resulted in significant decrease(P【0.05) in blood glucose level in a dose dependent manner by 36%,48%,and 64%at doses of 0.2,0.3 and 0.5 g/kg,respectively,in comparison to the STZ control values.Treatment with OS elicited an increase in the expression level of Slc2a2 gene but reduced the expression of G6Pase and PCK1 genes.Morefore,OS treated rats,showed significantly lower levels of serum alanine transaminase(ALT),aspartate aminotransferase(AST) and urea levels compared to STZ untreated rats.The extract at different doses elicited signs of recovery in body weight gain when compared to STZ diabetic controls although food and water consumption were significantly lower in treated groups compared to STZ diabetic control group.Conclusions:O.sumatrana aqueous extract is beneficial for improvement of hyperglycemia by increasing gene expression of liver Slc2a2 and reducing expression of G6Pase and PCK1 genes in streptozotocin-induced diabetic rats.展开更多
AIM： To study the histopathological changes in the retina and flash electroretinogram （F-ERG） features of ozone-treated streptozotocin （STZ）-induced diabetic rats. METHODS： Seventy male Sprague Dawley rats were ...AIM： To study the histopathological changes in the retina and flash electroretinogram （F-ERG） features of ozone-treated streptozotocin （STZ）-induced diabetic rats. METHODS： Seventy male Sprague Dawley rats were grouped as follows： blank group （GB, n=10）, model control group （GM, n=18）, ozone group （GOs, n=19）, and oxygen group （GO2, n=18）. The model was induced by single intraperitoneal injection of STZ. Ozone or oxygen enteroclysm was given twice per week for 4wk. F-ERG and histopathological examinations were performed one month after treatment. RESULTS： Under dark adaption, as compared to GB, the other groups each had differential decreases in the a-wave amplitudes （P〈0.05）; the latencies were delayed in GM, GO2, and GO3 rats （P〈0.05）. Similar results were observed under light adaption, with the exception that the a-wave of the amplitudes （F=0.28, P〉0.05）. There were significant differences in the apoptosis index among the groups （P〈0.05）. Under ozone treatment, apoptosis was decreased in GO3 as compared to GM and GO2 . CONCLUSION： Ozone administration alleviates nerve damage and reduces pathology and apoptosis in the retinas of diabetic rats.展开更多
文摘Background:Cucurbita maxima plant materials are frequently used to manage a number of disorders,according to previous studies.Objective:The goal of the present report was to look into further possible effects of this plant on kidney disorder in rats brought on by diabetes as well as the related abnormalities in lipid metabolism.Methods:To assess the ameliorative effect of the plant,streptozotocin(STZ)(45 mg/kg/day)was given as a single dosage to cause type 1 diabetes.After then,diabetic rats received supplemented diets of Cucurbita maxima for four weeks at 5%,10%,15%and 20%ad libidium.However,in another experiment to evaluate the preventive capacity of Cucurbita maxima,the STZ-induction came at the end of four weeks supplementation.Blood and kidney tissues were obtained at the end of the treatments and investigated.Consequently,the analysis of kidney function and lipid profile was made using serum obtained from the blood sample.Histological change in kidney was also observed using haematoxylin and eosin stain Results:Our findings demonstrated that Cucurbita maxima drastically(P<0.05)decreased the elevated kidney indicators such as urea and creatinine in the blood,and restored the electrolytes and lipid profiles anomalies as compared to the normal control.However,the alteration of biochemical parameters in the STZ-induced diabetic control remained unchanged throughout as compared to the normal control.The above mentioned biochemical changes that took place in kidney tissues were further corroborated by histological alterations.Conclusion:The results suggest that Cucurbita maxima leaves supplemented diets reversed STZ-induced renal disorder and abnormal lipid metabolism,and that these effects may be mediated by interacting with multiple receptors to raise the levels of antioxidant enzymes in the system.
文摘Research Background and Purpose: The number of diabetic patients is rapidly increasing, making it crucial to find methods to prevent diabetic retinopathy (DR), a leading cause of blindness. We investigated the effects of prophylactic pattern scanning laser retinal photocoagulation on DR development in Spontaneously Diabetic Torii (SDT) fatty rats as a new prevention approach. Methods: Photocoagulation was applied to the right eyes of 8-week-old Spontaneously Diabetic Torii (SDT) fatty rats, with the left eyes serving as untreated controls. Electroretinography at 9 and 39 weeks of age and pathological examinations, including immunohistochemistry for vascular endothelial growth factor and glial fibrillary acidic protein at 24 and 40 weeks of age, were performed on both eyes. Results: There were no significant differences in amplitude and prolongation of the OP waves between the right and left eyes in SDT fatty rats at 39 weeks of age. Similarly, no significant differences in pathology and immunohistochemistry were observed between the right and left eyes in SDT fatty rats at 24 and 40 weeks of age. Conclusion: Prophylactic pattern scanning retinal laser photocoagulation did not affect the development of diabetic retinopathy in SDT fatty rats.
基金Supported by grant from Fundamental Research Grant Scheme by Ministry of Higher Education(MoHE)600-IRMI/FRGS 5/3(101/2019).
文摘AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.
基金the grant from Technical Program of Social Development ofNantong Municipality (No.S30043)the Natural ScienceFoundation of Nantong University (No. 05Z084)
文摘Objective To screen and identify differentially expressed genes in the dorsal root ganglion （DRG） in early experimental diabetic rats. Methods Diabetic model rats were induced by single intraperitoneal injection of streptozotocin （STZ）. At the second week after STZ injection, the sensory nerve conduction velocities （SNCV） of sciatic nerve were measured as an indicator of neuropathy. The technique of silver-staining mRNA differential display polymerase chain reaction （DD-PCR） was used to detect the levels of differentially expressed genes in rat DRG. The cDNA fragments that displayed differentially were identified by reverse-hybridization, cloned and sequenced subsequently, and then confirmed by Northern blot. Results The SNCV in the diabetic model group [n = 9, （45.25±10.38） m/s] reduced obviously compared with the control group [n = 8, （60.10± 11.92） m/s] （P 〈 0.05）. Seven distinct cDNA clones, one was up-regulated gene and the others were downregulated ones, were isolated by silver-staining mRNA differential display method and confirmed by Northern blot. According to the results of sequence alignment with GenBank data, majority of the clones had no significant sequence similarity to previously reported genes except only one that showed high homology to 6-pyruvoyl-tetrahydropterin synthase mRNA （accession No., BC059140）, which had not been reported to relate to diabetic neuropathy. Conclusion These differentially expressed genes in the diabetic DRG may contribute to the pathogenesis of diabetic peripheral neuropathy.
基金This work was supported by the National Natural Science Foundation of China(No.30370467)the Bilateral Scientific and Technological Cooperation between Flanders and China(Contract BIL01/13).
文摘Objective To investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin （EM） on the regulation of gastric motility in diabetic rats. Methods The motilin immunoreactive neurons in the hypothalamus and the hippocampus were detected by immunohistochemistry with rabbit anti-motilin polyclonal antibody. To measure the gastric motility, force transducers were surgically affixed to the gastric serosa. A microinjection syringe was connected via a plastic tube to an injection cannula, which was connected with a stainless steel guide cannula. The syringe was inserted into the right lateral cerebral ventricle for microinjecting the chemicals. Results Diabetic mellitus was successfully induced in cohorts of rats. Motilin-immunoreactive neurons significantly increased in the paraventricular （PVN） and supraoptic nuclei （SON） of the hypothalamus in the diabetic rats. Intracerebroventricular （i.c.v.） administration of EM, a motilin receptor agonist, stimulated the gastric motility of diabetic rats. EM （91.56 nmol, i.c.v.） dose-dependently increased the amplitude by （174.82±48.62）% （P 〈 0.05）, and increased the frequency by （70.43±27.11）% （P 〈 0.05） in 5 min. The stimulatory effect lasted more than 15 min to the end of the measurement, and can be blocked partially by the prior treatment of motilin receptor antagonist GM-109. Conclusion Motilin-immunoreactive neurons are increased in the PVN and SON of the hypothalamus in diabetic rats. Centrally administered EM may regulate gastric motility by binding to the central motilin receptors, and central motilin might be involved in regulation of gastric motility in diabetic rats.
基金This research was supported by the Science Found of Zhejiang Province (No. 2004C32082)
文摘Objective To investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats. Methods Thirty Sprague-dawley female rats were randomly divided into three groups （n=10 each）, ＂control group＂ with intraperitoneal saline injection, ＂diabetic group＂ with 60 mg of intraperitoneal streptozotocin injection per kg of body weight and ＂Hsian-tsao group＂ with intragastric administration of Hsian-tsao extraction everyday for 4 weeks after intraperitoneal streptozotocin injection. The body weight and blood sugar were measured before and after model induction in the three groups. Thrombospondin-1 （TSP-1） expressions in the kidney were monitored by immunohistochemistry. Kidney ultrastructural changes were also analyzed by using transmission electron microscopy. Results Before diabetic model induction, there were no significant differences among the three groups in body weight and blood sugar. Four weeks after the induction of diabetes, the differences became statistically significant. Electron microscopy also revealed disruption of the foot processes of the podocytes and other damages in diabetic group. These damages were significantly less severe in Hsian-tsao group when compared with the diabetic group. TSP-1 expressions in the kidney were significantly increased in both the diabetic group and Hsian-tsao group, but it was relatively lower in Hsian-tsao group than in diabetic group. Conclusion Our results showed that Hsian-tsao treatment in the diabetic rats effectively prevented the pathological alterations in the kidney and decreased the TSP- 1 expression. It was suggested that Hsian-tsao had protective effect on the kidneys of the diabetic rats.
文摘Objective:To investigate the antidiabetic properties of aqueous extract of stem bark of Afzelia africana(A.africana)and its beneficial effect on haematological parameters in streptozotocin induced diabetic rats.Methods:A total of 30 rats including 24 diabetic and 6 normal rats were used for this study.Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin.After being confirmed diabetic,animals were orally treated with distilled water or extracts at 100 or 200 mg/kg body weight daily for 10 days.The haematological parameters including red blood and white blood cells and their functional indices were evaluated in diabetic treated groups compared with the controls.Results:The extract significantly reduced the blood glucose levels while the best result was obtained at 200 mg/kg body weight The feed and water intake in diabetic rats were significantly reduced while weight loss was minimized at both dosages.Similarly,the levels of red blood,white blood cells and their functional indices were significantly improved after extract administration at both doses.Conclusions:It can be concluded that the aqueous extract of bark of A.africana possesses antihyperglycemic properties.In addition,the extract can prevent various complications of diabetes and improve some haematological parameters.Further experimental investigation is needed to exploit its relevant therapeutic effect to substantiate its ethnomedicinal usage.
基金carried out through the funding Provided by CapePeninsula University of Technology,Bellville,South Africa(grant NO.NRF-CPUT/RJ24)
文摘Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was induced by a single administration of streptozotocin(50 mg/kg)and the rats were treated for 7 weeks.Antioxidant enzymes[calalase(CAT),glutathione peroxidase(GPx),superoxide dismutase(SOD)],antioxidant capacity[trolox equivalence antioxidant capacity(TEAC),oxygen radical absorbance capacity(ORAC)]as well as total protein,albumin,globulin,total glutathione,conjugated diene and thiobarbituric acid reactive substances(TBARS)were investigated.Results:Treatment with RPO,RTE and RPO+RTE significantly(p>0.05)improved liver SOD and plasma ORAC in the diabetic rats.Similarly,diabetic rats treated with RTE and RPO+RTE enhanced liver GPx.A significant(P<0.05)increase in the plasma TBARS in the diabetic control group was observed when compared with the normal control group.Treatment of diabetic rats with RTE and RPO+RTE reduced plasma TBARS to a level not significantly different at P<0.05 from the normal control group.Conclusions:The results revealed the anti-oxidative potentials of red palm oil,rooibos and their combination in diabetic conditions and hence,they could be useful in the management of diabetes and its complications.
基金Shahhag, Dhaka. Bangladesh, for providing technical moral ami financial support for this project
文摘Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P<0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P<0.07)but reduced glutathione content was found to be increased significantly(P<0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.
基金Supported by National Natural Science Foundation of China(No.81270999)the Key Project of Miaopu of Fujian Medical University(No.2015MP004)the Qihang Funds of Fujian Medical University(No.2018QH1063)
文摘AIM: To evaluate the effects of etanercept on the expression of Fas, tumor necrosis factor-alpha(TNF-α) and caspase-8 in the early stage of the apoptotic pathway in diabetic rats, and to explore the therapeutic effect of etanercept on diabetic retinopathy.METHODS: A total of 60 Sprague-Dawley(SD) rats were randomly and evenly divided into 3 groups with 20 rats each, including control group, and diabetic groups with or without treatment. Streptozotocin(STZ)-induced diabetic rats were established for diabetic groups. Blood glucose and body weight were measured weekly. All the rats were sacrificed at the 12 wk after treatment. The expressions of Fas, TNF-α and caspase-8 in rat retina were quantitatively detected by PCR and Western blot. The leakage of Evan blue was adopted to measure the retinal vascular leakage quantitatively, and to compare it among different groups. TUNEL method was used to compare the amount of apoptotic bodies quantitatively in rat retina ganglion cells under electron microscope.RESULTS: The expressions of Fas, TNF-α and caspase-8 in each group were compared via PCR and Western blot, in which the diabetic group with treatment was lower than those without treatment(P<0.01), but all the diabetic groups were higher than the control group(P<0.01). Evans blue leakage in the diabetic treatment group was lower than those without treatment(P<0.01), but those in the control group was the lowest compared with the other two groups(P<0.01). TUNEL method showed that the apoptoticbodies of retina in the diabetic treatment group was lower than those without treatment(P<0.01), while those in the control group was the lowest compared with the other two groups(P<0.01). CONCLUSION: Etanercept can effectively reduce the expression of Fas, TNF-α and caspase-8, as well as the retinal leakage and retinal cell apoptosis in diabetic rats.
文摘An Otsuka Long-Evans Tokushima Fatty(OLETF)rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.We investigated the effects of sericin on corneal wound healing in OLETF rats.Corneal wounds were prepared by removal of the corneal epithelium and documented using a TRC-50X.Sericin was instilled into the eyes of rats five times a day following corneal abrasion.The plasma levels of glucose,triglycerides,cholesterol and insulin in 38 wk old OLETF rats were significantly higher than in normal control rats(LETO rats),and the rate of corneal wound healing in OLETF rats was slower than in normal rat,probably due to the suppression of cell migration and proliferation caused by high plasma glucose levels.The corneal wounds of OLETF rats instilled with saline showed almost complete healing 72h after corneal epithelial abrasion.On the other hand,the instillation of sericin has a potent effect in promoting wound healing and wound size reduction in OLETF rats and the wounds showed almost complete healing at 48 h after abrasion.The sericin may be an effective and safe drug to promote corneal wound healing in diabetic keratopathy.
基金Supported by National Natural Science Fundation of China (No.81303282)Central Finance of China in Support of the Development of Local Colleges and University [Educational Finance Grant No.338 (2013/2014)]+1 种基金Department of Education of Guangdong Province (No.Yq2013044)Science and Information Technology of Guangzhou (No.2013J2200034)
文摘AIM: To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type -2 diabetes, and then to investigate the mechanisms. METHODS: ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS: DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c 1094 (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION: DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism.
文摘AIM： To investigate the effect of a Chinese medicine, Kaiyu Qingwei Jianji （KYQWJJ） used for diabetic treatment, on the morphometry and residual strain distribution of the small intestine in streptozotocin （STZ） -induced diabetic rats. Correlation analysis was also performed between the opening angle and residual strain with the blood glucose level. METHODS： Forty-two male Wistar rats weighing 220-240 g were included in this study. Thirty-two STZ- induced diabetic rats were subdivided into four groups （n = 8 in each group）, i.e. diabetic control group （DM）; high dose of KYQWJJ （T1, 36g/kg per day）; low dose of KYQWJJ （T2, 17 g/kg per day） and Gliclazide （T3, 50 mg/kg per day）. Another ten rats were used as nondiabetic control （CON）. The medicines were poured directly into stomach lumen by gastric lavage twice daily. The rats of CON and DM groups were only poured the physiological saline. Blood glucose and plasma insulin levels were measured. Experimental period was 35 d. At the end of experiment, three 5-cm long segments were harvested from the duodenum, jejunum and ileum. Three rings of 1-2 mm in length for no-load and zero-stress state tests were cut from the middle of different segments. The morphometric data, such as the circumferential length, the wall thickness and the opening angle were measured from the digitized images of intestinal segments in the no-load state and zerostress state. The residual strain was computed from the morphometry data. Furthermore, the linear regression analysis was performed between blood glucose level with morphometric and biomechanical data in the different intestinal segments. RESULTS： The blood glucose level of DM group was consistent 4-fold to 5-fold higher than those in CON group during the experiment （16.89 ± 1.11 vs 3.44 ± 0.15 mmol/L, P 〈 0.001）. The blood glucose level in the T1 （16.89 ± 1.11 vs 11.08 ± 2.67 mmol/L, P 〈 0.01） and T3 groups （16.89 ± 1.11 vs 13.54 ± 1.73 mmol/L, P 〈 0.05）, but not in T2 group （P 〉 0.05） was significantly lower than those in DM group. The plasma insulin levels of DM, T1, T2 and T3 groups were significantly lower than those in CON group （10.98 ± 1.02, 12.52 ± 1.42,13.54 ± 1.56,10.96 ± 0.96 vs 17.84 ± 2.34 pmol/L respectively, P 〈 0.05）, but no significantly difference among the groups with exception of CON group. The wet weight/cm and total wall thickness of duodenum, jejunum and ileum in DM group were significantly higher than those in CON group （wet weight （g/cm）： duodenum 0.209 ± 0.012 vs 0.166 ± 0.010, jejunum 0.149 ± 0.008 vs 0.121 ± 0.004, ileum 0.134 ± 0.013 vs 0.112 ± 0.007; Wall thickness （mm）： duodenum 0.849 ± 0.027 vs 0.710 ± 0.026, jejunum 0.7259 ± 0.034 vs 0.627 ± 0.025, ileum 0.532 ± 0.023 vs 0.470 ± 0.010, all P 〈 0.05）, T1 and T3 treatment could partly restore change of wall thickness, but T2 could not. The opening angle and absolute value of inner and outer residual stain were significantly smaller in duodenal segment （188 ± 11 degrees, -0.31 ± 0.02 and 0.35 ± 0.03 vs 259 ± 15 degrees, -0.40 ± 0.02 and 0.43 ± 0.05） and larger in jejunal （215 ± 20 degrees, -0.30 ± 0.03 and 0.36 ± 0.06 vs 172 ± 19 degrees, -0.25 ± 0.02 and 0.27 ± 0.02） and ileal segments （183 ± 20 degrees, -0.28 ± 0.01 and 0.34 ± 0.05 vs 153 ± 14 degrees, -0.23 ± 0.03 and 0.29 ± 0.04） in DM group than in CON group （P 〈 0.01）. TI and T3 treatment could partly restore this biomechanical alteration, but strong effect was found in T1 treatment （duodenum 243 ± 14 degrees, -0.36 ± 0.02 and 0.42 ± 0.06, jejunum 180 ± 15 degrees, -0.26 ± 0.03 and 0.30 ± 0.06 and ileum 163 ± 17 degrees, -0.23 ± 0.03 and 0.30 ± 0.05, compared with DM, P 〈 0.05）. The linear association was found between the glucose level with most morphometric and biomechanical data. CONCLUSION： KYQWJJ （high dose） treatment could partly restore the changes of blood glucose level and the remodeling of morphometry and residual strain of small intestine in diabetic rats. The linear regression analysis demonstrated that the effect of KYQWJJ on intestinal opening angle and residual strain is partially through its effect on the blood glucose level.
基金Supported by the Special Research Fund, Account Code: 4280, National and Kapodistrian University of Athens, Greece
文摘AIM: To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. METHODS: Thirty-six male Wistar rats and 18 male Lewis rats were used as recipients and donors respectively. Diabetes was induced by the use of streptozotocin (60 mg/kg) intraperitoneally. Unpurified islets were isolated using the collagenase digestion technique and transplanted into the splenic parenchyma. The recipients were randomly assigned to one of the following three groups: group A (control group) had no immunosuppression; group B received cyclosporine (CsA) (5 mg/kg); group C receivedmycophenolate mofetil (MMF) (20 mg/kg). The animalswere killed on the 12th d. Blood and grafted tissues were obtained for laboratory and histological assessment. RESULTS: Median allograft survival was significantly higher in the two therapy groups than that in the controls (10 and 12 d for CsA and MMF respectively vs 0 d for the control group, P＜0.01). No difference in allograft survival between the CsA and MMF groups was found. However,MMF had less renal and hepatic toxicity and allowed weight gain.CONCLUSION: Monotherapy with MMF for immunosu ppression was safe in an experimental model of islet allotransplantation and was equally effective with cyclosporine, with less toxicity.
文摘AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced diabetic SpragueDawley(SD) rat model.METHODS: SD rats were administered an abdominal injection of STZ and induced to a diabetic model. After 6 wk course of diabetes, the treatment groups were given β-elemene through periocular and intravitreous injection separately and the control groups were given blank emulsion injection. HE staining was used to observe the morphology of retina. The m RNA expressions of HIF-1α, VEGF and i NOS was assayed by real-time polymerase chain reaction(PCR) and the protein expression was measured by Western blot and immunocytochemistry methods.RESULTS: The results indicated that the protein and m RNA expressions of HIF-1α, VEGF and i NOS after treated by β-elemene periocularly and intravitreally injections were all found to be reduced compared with the levels in the diabetic rats group(P<0.05). The inhibitory effect of intravitreal injection was more remarkable.CONCLUSION: The results show β-elemene protect the retina of diabetic rats from high glucose damage by downregulating the expression of HIF-1α, VEGF and iNOS.
基金Supported by Biomedical Research Institute Grant(PNU-2013-0373),Pusan National University Hospital
文摘AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.
基金Supported by National Natural Science Foundation of China,No. 81173259/H2708
文摘AIM： To investigate the effect of Tangweian Jianji （TWAJJ） on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats. METHODS： Diabetes was induced in 27 rats by in- jecting streptozotocin （40 mg/kg body weight）, the animals were then divided into three groups （n = 9 in each group）, i.e., diabetic control （DM）; high dose （10 g/kg, T1） and low dose （5 g/kg, T2）. Another 10 rats acted as normal controls （Control）. TWAJJ was admin- istered by gavage once daily. Blood glucose and serum insulin levels were measured. Circumferential length, wall thickness and opening angle were measured from esophageal, duodenal, jejunal and ileal ring segments. The residual strain was calculated from the morpho- metric data. Step-wise distension was carried out on esophageal and jejunal segments. The obtained data on the length, diameter and pressure changes were then used to calculate the circumferential and longitu- dinal stresses and strains. Real-time reverse transcrip- tion polymerase chain reaction was used to detect the receptor of advanced glycation end-products （RAGE） mRNA level in jejunal tissues. RESULTS： At the end of the experiment, the blood glucose level was significantly higher and the serum insulin level was significantly lower in DM, T1 and T2 groups than in the control group （Glucose： 30.23 ± 0.41 mmol/L, 27.48 ± 0.27 mmol/L and 27.84 ± 0.29 mmol/ L vs 5.05 ± 0.04 mmol/L, P = 1.65 x 10-16, P = 5.89 x 1019 and P = 1.63 x 10-Is, respectively; Insulin： 1.47 ± 0.32 °tg/L, 2.66 ± 0.44 pg/L, 2.03 ± 0.29 pg/L and 4.17 ± 0.54 pg/L, P = 0.0001, P = 0.029 and P = 0.025, re- spectively）. However, these levels did not differ among the DM, T1 and T2 groups. The wet weight per unit length, wall thickness and opening angle of esophageal and intestinal segments in the DM group were signifi- cantly higher than those in the control group （from P = 0.009 to P = 0.004）. These parameters in the T1 group were significantly lower than those in the DM group （wet weight, duodenum： 0.147 ± 0.003 g/cm vs 0.158 ± 0.001 g/cm, P = 0.047; jejunum, 0.127 ± 0.003 g/cm vs 0.151：1：0.002 g/cm, P = 0.017; ileum, 0.127 ± 0.004 g/cm vs 0.139 ± 0.003 g/cm, P = 0.046; wall thickness, esophagus： 0.84±0.03 mm vs 0.94 ± 0.02 ram, P = 0.014; duodenum： 1.27 ± 0.06 mm vs 1.39 ± 0.05 ram, P = 0.031; jejunum： 1.19 ± 0.07 mm vs 1.34 ± 0.04 mm, P = 0.047; ileum： 1.09 ± 0.04 mm vs 1.15 ± 0.03 mm, P = 0.049; opening angle, esophagus： 112.2 ± 13.2° vs 134.7 ± 14.7°, P = 0.027; duodenum： 105.9 ± 12.3° vs 123.1 ± 13.1°, P = 0.046; jejunum： 90.1 ± 15.4° vs 115.5 ± 13.3°, P = 0.044; ileum： 112.9 ± 13.4° vs 136.1 ± 17.1°, P = 0.035）. In the esophageal and jejunal segments, the inner residual stain was significantly smaller and the outer residual strain was larger in the DN group than in the control group （P = 0.022 and P = 0.035）. T1 treatment significantly restored this biomechanical alteration （P = 0.011 and P = 0.019）, but T2 treatment did not. Fur- thermore, the circumferential and longitudinal stiffness of the esophageal and jejunal wall increased in the DM group compared with those in the control group. T1, but not T2 treatment, significantly decreased the cir- cumferential wall stiffness in the jejunal segment （P = 0.012） and longitudinal wall stiffness in the esophageal segment （P = 0.023）. The mRNA level of RAGE was significantly decreased in the T1 group compared to that in the DN group （P = 0.0069）. CONCLUSION： TWAJJ （high dose） treatment partly restored the morphometric and biomechanical remodel- ing of the upper gastrointestinal tract in diabetic rats.
文摘AIM:To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions.METHODS:Seven diabetic Goto-Kakizaki(GK)male rats,32-wk old(GK group),and 9 age-matched normal Wistar rats(Normal group)were included in the study.Jejunal segments were distended up to a pressure of10 cm H2O in an organ bath containing 37℃Krebs solution with addition of carbachol(CA).The pressure and outer diameter changes were synchronously recorded.Passive conditions were obtained using calcium-free Krebs solution containing ethylene glycol tetraacetic acid and papaverine.Total phasic,tonic and passive circumferential stress and strain were computed from the diameter and pressure data with reference to the zero-stress state geometry.The active phasic and tonic stresses were defined as the total phasic and tonic stresses minus the passive stress.RESULTS:Diabetes increased jejunal mucosa and muscle layer thicknesses compared to the Normal group(mucosa,755.8±63.3 vs 633.1±59.1μm,P<0.01;muscle,106.3±12.9 vs 85.2±11.7μm,P<0.05).The pressure and stress thresholds were decreased in the GK group after CA application compared to distensions without CA application(pressure,1.01±0.07vs 1.99±0.19 cmH2O,P<0.01;stress,0.11±0.01vs 0.24±0.02 kPa,P<0.01).CA application did not change the pressure and stress threshold in the Normal group(pressure,2.13±0.32 vs 2.34±0.32 cm H2O,P>0.05;stress,0.25±0.03 vs 0.35±0.06 kPa,P>0.05).The amplitude of total phasic,total tonic,active phasic and active tonic circumferential stresses did not differ for the distensions without CA application between the GK group and the Normal group.However,the total phasic and total tonic stresses increased after CA application in the GK group compared those in the Normal group.When normalized to muscle layer thickness,the amplitude of active stresses before CA application was lowest in the GK group compared with the Normal group.No difference was found during CA application.CONCLUSION:The stress generated by intestinal muscle normalized to the muscle layer thickness was lowest in GK rats compared to normal rats whereas the response to CA stimulation was preserved.
文摘Objective:To investigate the hypoglycemic effect of the aqueous extract of Octomeles sumatrana (O.sumatrana)(OS) in streptozotocin-induced diabetic rats(STZ) and its molecular mechanisms. Methods:Diabetes was induced by intraperitoneal(i.p.) injection of streptozotocin(55 mg/kg) in to male Sprague-Dawley rats.Rats were divided into six different groups;normal control rats were not induced with STZ and served as reference,STZ diabetic control rats were given normal saline.Three groups were treated with OS aqueous extract at 0.2,0.3 and 0.5 g/kg,orally twice daily continuously for 21 d.The fifth group was treated with glibenclamide(6 mg/kg) in aqueous solution orally continuously for 21 d.After completion of the treatment period,biochemical parameters and expression levels of glucose transporter 2(Slc2a2),glucose-6-phosphatase (GoPase) and phosphoenolpyruvate carboxykinase(PCK1) were determined in liver by quantitative real time PCR.Results:Administration of OS at different doses to STZ induced diabetic rats, resulted in significant decrease(P【0.05) in blood glucose level in a dose dependent manner by 36%,48%,and 64%at doses of 0.2,0.3 and 0.5 g/kg,respectively,in comparison to the STZ control values.Treatment with OS elicited an increase in the expression level of Slc2a2 gene but reduced the expression of G6Pase and PCK1 genes.Morefore,OS treated rats,showed significantly lower levels of serum alanine transaminase(ALT),aspartate aminotransferase(AST) and urea levels compared to STZ untreated rats.The extract at different doses elicited signs of recovery in body weight gain when compared to STZ diabetic controls although food and water consumption were significantly lower in treated groups compared to STZ diabetic control group.Conclusions:O.sumatrana aqueous extract is beneficial for improvement of hyperglycemia by increasing gene expression of liver Slc2a2 and reducing expression of G6Pase and PCK1 genes in streptozotocin-induced diabetic rats.
基金Supported by the Xinjiang Natural Science Research Fund (No. 2014211C046)
文摘AIM： To study the histopathological changes in the retina and flash electroretinogram （F-ERG） features of ozone-treated streptozotocin （STZ）-induced diabetic rats. METHODS： Seventy male Sprague Dawley rats were grouped as follows： blank group （GB, n=10）, model control group （GM, n=18）, ozone group （GOs, n=19）, and oxygen group （GO2, n=18）. The model was induced by single intraperitoneal injection of STZ. Ozone or oxygen enteroclysm was given twice per week for 4wk. F-ERG and histopathological examinations were performed one month after treatment. RESULTS： Under dark adaption, as compared to GB, the other groups each had differential decreases in the a-wave amplitudes （P〈0.05）; the latencies were delayed in GM, GO2, and GO3 rats （P〈0.05）. Similar results were observed under light adaption, with the exception that the a-wave of the amplitudes （F=0.28, P〉0.05）. There were significant differences in the apoptosis index among the groups （P〈0.05）. Under ozone treatment, apoptosis was decreased in GO3 as compared to GM and GO2 . CONCLUSION： Ozone administration alleviates nerve damage and reduces pathology and apoptosis in the retinas of diabetic rats.
