Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cereb...Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expre...Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.展开更多
Introduction: Renal ischemia-reperfusion (IR) is responsible for injuries such as destruction or dysfunction of tubular epithelial cells with inflammatory reaction and oxidative stress. Several therapeutic methods hav...Introduction: Renal ischemia-reperfusion (IR) is responsible for injuries such as destruction or dysfunction of tubular epithelial cells with inflammatory reaction and oxidative stress. Several therapeutic methods have been tested to alleviate ischemia-perfusion injury, ranging from using anti-inflammatory drugs, antioxidants, and plants from traditional pharmacopeia to administering RNA interference. However, there is currently no effective therapeutic option available for the treatment of renal IR injury, other than supportive therapies such as renal replacement therapy or hydration. Objective: This present study aimed to evaluate the effect of Guiera senegalensis on renal ischemia reperfusion, a recognized plant for its antioxidant and anti-inflammatory properties. Materials and Methods: Twenty-four (24) adult male Wistar rats were divided into four following groups: SLAM (subjected to a median laparotomy with simulated ischemia);GUIERRA (animals that received 250 mg/kg of guierra senegalensis orally, once a day, for 5 days, with simulated renal ischemia);IR (animals that underwent laparotomy followed by clamping of bilateral renal pedicles for 45 min and followed by reperfusion);GUIERRA + IR (animals given GUIERRA at the dosage of 250 mg/kg per day, for 5 days and then subjected to renal ischemia-reperfusion). Data analysis was performed by ANOVA, and a significance level of p Results: Compared with the I/R group, rats in the GUIERRA + IR group showed reduced histopathological damage scores (p Conclusion: The results of this preliminary work suggest that Guiera senegalensis decreases the degree of tissue damage in renal ischemia-reperfusion cases. This plant seems to be a promising therapeutic;further studies could help to precise the targets of its compounds on ischemia-reperfusion pathways.展开更多
With the wide application of thrombolytic drugs and the advancement of endovascular therapeutic techniques, the recanalization treatment of acute artery occlusion in ischemic stroke (IS) has made a leap forward, but i...With the wide application of thrombolytic drugs and the advancement of endovascular therapeutic techniques, the recanalization treatment of acute artery occlusion in ischemic stroke (IS) has made a leap forward, but ischemic brain tissues still face ischemia-reperfusion injury after recanalization. Nowadays, effective neurological protective agents still cannot completely resist the multiple damages of ischemia-reperfusion injury. As an iron-dependent mode of programmed cell death, ferroptosis occupies an important position in ischemia-reperfusion injury. Selenium plays a unique protective role in ischemia-reperfusion injury as an active site element in the center of glutathione peroxidase. Therefore, the study mainly aims to review the protective role of selenium in IS and the related mechanisms, as well as the effect of selenium on the risk factors of IS.展开更多
β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unkno...β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.展开更多
Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Curre...Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Current studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion injury.However,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration.In this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and autophagy.The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box O.This review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins expression.This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors.While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug therapies.Overall,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.展开更多
Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of...Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.展开更多
Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in ...Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.展开更多
Ischemia/reperfusion(I/R)injury ismarked by the restriction and subsequent restoration of blood supply to an organ.This process can exacerbate the initial tissue damage,leading to further disorders,disability,and even...Ischemia/reperfusion(I/R)injury ismarked by the restriction and subsequent restoration of blood supply to an organ.This process can exacerbate the initial tissue damage,leading to further disorders,disability,and even death.Extracellular vesicles(EVs)are crucial in cell communication by releasing cargo that regulates the physiological state of recipient cells.The development of EVs presents a novel avenue for delivering therapeutic agents in I/R therapy.The therapeutic potential of EVs derived from stem cells,endothelial cells,and plasma in I/R injury has been actively investigated.Therefore,this review aims to provide an overview of the pathological process of I/R injury and the biophysical properties of EVs.We noted that EVs serve as nontoxic,flexible,and multifunctional carriers for delivering therapeutic agents capable of intervening in I/R injury progression.The therapeutic efficacy of EVs can be enhanced through various engineering strategies.Improving the tropism of EVs via surface modification and modulating their contents via preconditioning are widely investigated in preclinical studies.Finally,we summarize the challenges in the production and delivery of EV-based therapy in I/R injury and discuss how it can advance.This review will encourage further exploration in developing efficient EV-based delivery systems for I/R treatment.展开更多
AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for a...AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.展开更多
Subjective: This study aimed to investigate the therapeutic mechanisms of 7-hydroxyflavone (7-HF) in treating myocardial ischemia/reperfusion injury (MI/RI) via network pharmacology, molecular docking, target validati...Subjective: This study aimed to investigate the therapeutic mechanisms of 7-hydroxyflavone (7-HF) in treating myocardial ischemia/reperfusion injury (MI/RI) via network pharmacology, molecular docking, target validation, and experiments at the animal level. Methods: Firstly, the genes of 7-HF were acquired from PharmMapper, TCMSP, and SwissTargetPrediction. At the same time, MI/RI-related genes were obtained from OMIM, GeneCards, and TTD online platforms. Subsequently, string platform and Cytoscape 3.9.2 were used to construct protein-protein interaction network diagrams and 7-HF-targets-signaling pathways-MI/RI network. Then, the Metascape platform was used to conduct functional enrichment analyses. Next, AutoDock Vina and Pymol were used to perform molecular docking. The hub targets were validated in the GSE66360. Lastly, SOD, MDA, transmission electron microscope, quantitative real-time PCR, and western blot were used to validate in MI/RI rats. Results: 139 genes of 7-HF, 4832 genes of MI/RI were obtained. The 47 interact genes between 7-HF and MI/RI targets for MI/RI were likely to act through multiple pathways. And NQO1 was a critical target in the above process. In an animal experiment, 7-HF could relieve the injured interfibrillar mitochondria and myocardial fibers, decrease the expression of MDA and SOD, and increase the expression of Nrf2, NQO1 and HO-1 in the mRNA and protein level in the MI/RI rats. Conclusion: This study preliminarily demonstrated that 7-HF could provide cardioprotection by inhibiting the oxidative stress and up-regulating Nrf2/NQO1/HO-1 signaling pathway based on network pharmacology, molecular docking, target validation, and animal experiments.展开更多
This study aimed to investigate the protective effects of zin-giberis and acniti praeparatae decoction on oxidative stress injury induced by my-ocardial ischemia reperfusion in rats. [Method] Myocardial ischemia-reper...This study aimed to investigate the protective effects of zin-giberis and acniti praeparatae decoction on oxidative stress injury induced by my-ocardial ischemia reperfusion in rats. [Method] Myocardial ischemia-reperfusion was performed by ligation of the left anterior descending coronary artery for 30 min, fol-lowed by reperfusion for 60 min. The effects of zingiberis and acniti praeparatae decoction on ECG ST segment, myocardial infarction percentage, malondialdehyde （MDA） content in the serum, superoxide dismutase （SOD） activity and other indica-tors were observed. [Result] Zingiberis and acniti praeparatae decoction could effec-tively inhibit ECG ST segment elevation caused by myocardial ischemia-reperfusion injuries, reduce the percentage of myocardial infarction, decline the content of MDA in the serum, and increase the activity of SOD. [Conclusion] Zingiberis and acniti praeparatae decoction exhibits protective effects on oxidative injuries caused by my-ocardial ischemia-reperfusion injuries in rats, which may be involved in reducing the formation of myocardial free radicals and enhancing antioxidant capacity of my-ocardium.展开更多
Ligustrazine （2,3,5,6-tetramethylpyrazine） is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mecha- nism of action of ligustraz...Ligustrazine （2,3,5,6-tetramethylpyrazine） is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mecha- nism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administra- tion, and the most effective mode of administration for clinical treatment of cerebral ischemia/ reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine admin- istration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[（1,1-dimethylethyl）oxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC 195 after cerebral ischemia were better than ligustrazine.展开更多
Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival...Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling pathway.This review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases.展开更多
AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expres...AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expression and cell apoptosiswere detected in rat model of hepatic/ renalischemia-reperfusion injury.ELISA,immunohist-ochemistry and TUNEL were used.Someischemia-reperfusion rats were treated with anti-P-selectin mAb.RESULTS Hepatic/renal function insuffic-iency,up-regulated expression of P-selectin inplasma and hepatic/renal tissue,hepatic/renalhistopathological damages and cell apoptosiswere found in rats with hepatic/renal ischemia-reperfusion injury,while these changes becameless conspicuous in animals treated with anti-P-selectin mAb.CONCLUSION P-selectin might mediateneutrophil infiltration and cell apoptosis andcontribute to hepatic/renal ischemia-reperfusioninjury,anti-P-selectin mAb might be an efficientapproach for the prevention and treatment ofhepatic/renal ischemia-reperfusion injury.展开更多
IM To observe the kinetics of D()lactate alteration in both portal and systemic circulations, and its relationship with intestinal injury in rats subjected to acute intestinal ischemiareperfusion.METHODS Anesthetize...IM To observe the kinetics of D()lactate alteration in both portal and systemic circulations, and its relationship with intestinal injury in rats subjected to acute intestinal ischemiareperfusion.METHODS Anesthetized rats underwent 75min superior mesenteric artery occlusion followed by 6hour reperfusion. Plasma D()lactate levels were measured by an enzymatic spectrophotometric assay.RESULTS Intestinal ischemia for 75 min resulted in a significant elevation of D()lactate levels in portal vein as compared with the baseline values (P<005). Plasma D()lactate levels had a tendency to further increase after reperfusion up to 6 hours. Similar alterations in D()lactate were also found in systemic circulation, there were no significant differences between the portal and systemic circulations at any time point. Moreover, the macropathological evaluation scores were significantly correlated to the portal D()lactate levels in animals at various time points (r=0415, P<001). In addition,there was a remarkable rise of endotoxin concentration within the portal vein at the end of 75min ischemia (P<005), reaching a peak at 2 hours postreperfusion.CONCLUSION Acute intestinal ischemia is associated with failure of mucosal barrier resulting in increased plasma D()lactate levels in both portal and systemic blood. The subsequent reperfusion might further increase D()lactate levels, which are correlated to the macropathological alterations. Plasma D()lactate may be a useful marker of intestinal injury following both ischemia and reperfusion insults.展开更多
Objective:To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury.Methods:A total of 48 male SD rats were randomly divided into control group(A),I/R group(B),high dose of rosiglitazone(...Objective:To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury.Methods:A total of 48 male SD rats were randomly divided into control group(A),I/R group(B),high dose of rosiglitazone(C),low dose of rosiglitazone(D).Plasm concentration of creatine kinase(CK),CK-MB,hsCRP,Superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),nitric oxide(NO)and endothelin(ET)were measured 1 h later after I/R.24 h after I/R hearts were harvested to observe pathological and ultrastructural changes.Immunohistochemistry and western blotting was used to test CD40 expression in myocardial tissue.Area of myocardial infarction were tested,arrhythmia rate during I/R was recorded.Results:Plasm concentration of creatine kinase(CK),CK-MB,hsCRP,NO,MDA and ET were decreased in group C,D compared with group B.Plasm concentration of T-SOD and GSHPx was increased significantly in group C,D compared with group B.Compared with group B,pathological and ultrastructural changes in group C,D were slightly.Myocardial infarction area and arrhythmia rate were lower in group C,D compare with group B.Conclusions:Rosiglitazone can protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration,inhibit inflammatory reaction,improve endothelial function,reduce oxidative stress and calcium overload.展开更多
Objective:To study the protective effect of hyperoside(Hyp) on cardiac ischemia reperfusion injury and its potential mechanism.Methods:Rats were divided into two groups for the evaluation,the Hyp(50 uM Hyp;n=8) and th...Objective:To study the protective effect of hyperoside(Hyp) on cardiac ischemia reperfusion injury and its potential mechanism.Methods:Rats were divided into two groups for the evaluation,the Hyp(50 uM Hyp;n=8) and the control group(n=8).Rat hearts were isolated and perfused with Krebs-Henseleit buffer(KHB) for 30 min.After being inhibited with cardioplegic solution,they were stored for 4 h in B21 solution at 4℃.Afterwards,rat hearts were perfused with KHB again for 45 min.In this period.Hyp was added into solutions of cardioplegia for storage and KHB.Parameters of cardiac functions,including heart rate,the systolic pressure of the left ventricle,the end-diastolic pressure of the left ventricle,the developed pressure of the left ventricle,the left-ventricular systolic pressure and the peak rise rate of the pressure of the left ventricle were recorded.The levels of adenosine triphosphate(ATP),the content of malondialdehyde and apoptotic cells were determined to evaluate the protective effect of Hyp on hearts suffered from ischemia reperfusion injury.Moreover,cultured cardiac myocytes were subjected to the process simulating ischemia/reperfusion.What were analyzed included the endoplasmic reticulum(ER) stress hallmarks expressions,such as binding immunoglobulin protein and C/EBP homologous protein,using the western blot and real-time PCR.Besides,the NF-E2-related factor 2(Nrf2) expression was measured to explore the potential mechanism.Results:Compared with the control group,the Hyp group had better cardiac functional parameters and higher ATP levels;pretreatment of Hyp greatly relieved the apoptosis of myocyte,decreased oxidative stress as well as ER stress and activated the signaling pathway of anti-oxidative Nrf2 to a further extent.Conclusions:Hyp plays an important role in preserving cardiac function by improving ATP levels of tissue,easing oxidative injury of myocardium and reducing apoptosis following IRI dramatically,while the ER stress inhibition and the downstream Nrf2 signaling activation may contribute to the effects of protection.展开更多
Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mech...Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/ reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-de- pendently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reper- fusion injury. These findings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82260245(to YX),81660207(to YX),81960253(to YL),82160268(to YL),U1812403(to ZG)Science and Technology Projects of Guizhou Province,Nos.[2019]1440(to YX),[2020]1Z067(to WH)+1 种基金Cultivation Foundation of Guizhou Medical University,No.[20NSP069](to YX)Excellent Young Talents Plan of Guizhou Medical University,No.(2022)101(to WH)。
文摘Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
文摘Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.
文摘Introduction: Renal ischemia-reperfusion (IR) is responsible for injuries such as destruction or dysfunction of tubular epithelial cells with inflammatory reaction and oxidative stress. Several therapeutic methods have been tested to alleviate ischemia-perfusion injury, ranging from using anti-inflammatory drugs, antioxidants, and plants from traditional pharmacopeia to administering RNA interference. However, there is currently no effective therapeutic option available for the treatment of renal IR injury, other than supportive therapies such as renal replacement therapy or hydration. Objective: This present study aimed to evaluate the effect of Guiera senegalensis on renal ischemia reperfusion, a recognized plant for its antioxidant and anti-inflammatory properties. Materials and Methods: Twenty-four (24) adult male Wistar rats were divided into four following groups: SLAM (subjected to a median laparotomy with simulated ischemia);GUIERRA (animals that received 250 mg/kg of guierra senegalensis orally, once a day, for 5 days, with simulated renal ischemia);IR (animals that underwent laparotomy followed by clamping of bilateral renal pedicles for 45 min and followed by reperfusion);GUIERRA + IR (animals given GUIERRA at the dosage of 250 mg/kg per day, for 5 days and then subjected to renal ischemia-reperfusion). Data analysis was performed by ANOVA, and a significance level of p Results: Compared with the I/R group, rats in the GUIERRA + IR group showed reduced histopathological damage scores (p Conclusion: The results of this preliminary work suggest that Guiera senegalensis decreases the degree of tissue damage in renal ischemia-reperfusion cases. This plant seems to be a promising therapeutic;further studies could help to precise the targets of its compounds on ischemia-reperfusion pathways.
文摘With the wide application of thrombolytic drugs and the advancement of endovascular therapeutic techniques, the recanalization treatment of acute artery occlusion in ischemic stroke (IS) has made a leap forward, but ischemic brain tissues still face ischemia-reperfusion injury after recanalization. Nowadays, effective neurological protective agents still cannot completely resist the multiple damages of ischemia-reperfusion injury. As an iron-dependent mode of programmed cell death, ferroptosis occupies an important position in ischemia-reperfusion injury. Selenium plays a unique protective role in ischemia-reperfusion injury as an active site element in the center of glutathione peroxidase. Therefore, the study mainly aims to review the protective role of selenium in IS and the related mechanisms, as well as the effect of selenium on the risk factors of IS.
基金supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL)China Postdoctoral Science Foundation,No.2020M683750(to LY)partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).
文摘β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
文摘Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Current studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion injury.However,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration.In this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and autophagy.The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box O.This review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins expression.This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors.While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug therapies.Overall,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.
基金supported by the National Natural Science Foundation of China,Nos.82102295(to WG),82071339(to LG),82001119(to JH),and 81901994(to BZ).
文摘Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.
基金supported by the Youth Development Project of Air Force Military Medical University,No.21 QNPY072Key Project of Shaanxi Provincial Natural Science Basic Research Program,No.2023-JC-ZD-48(both to FF)。
文摘Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.
基金This work was supported by the National Natural Science Foundation of China(U22A20383,82003668)the Natural Science Foundation of Zhejiang Province(LD22H300002,LQ21H300002)Ningbo Technology Innovation 2025 Major Special Project(2022Z150).
文摘Ischemia/reperfusion(I/R)injury ismarked by the restriction and subsequent restoration of blood supply to an organ.This process can exacerbate the initial tissue damage,leading to further disorders,disability,and even death.Extracellular vesicles(EVs)are crucial in cell communication by releasing cargo that regulates the physiological state of recipient cells.The development of EVs presents a novel avenue for delivering therapeutic agents in I/R therapy.The therapeutic potential of EVs derived from stem cells,endothelial cells,and plasma in I/R injury has been actively investigated.Therefore,this review aims to provide an overview of the pathological process of I/R injury and the biophysical properties of EVs.We noted that EVs serve as nontoxic,flexible,and multifunctional carriers for delivering therapeutic agents capable of intervening in I/R injury progression.The therapeutic efficacy of EVs can be enhanced through various engineering strategies.Improving the tropism of EVs via surface modification and modulating their contents via preconditioning are widely investigated in preclinical studies.Finally,we summarize the challenges in the production and delivery of EV-based therapy in I/R injury and discuss how it can advance.This review will encourage further exploration in developing efficient EV-based delivery systems for I/R treatment.
基金Supported by the National Natural Science Foundation of China(No.82071888)the Natural Science Foundation of Shandong Province(No.ZR2021MH351,No.ZR2020MH074)+1 种基金the Introduction and Cultivation Project for Young Innovative Talents in Shandong ProvinceWeifang Science and Technology Development Plan(No.2021GX057).
文摘AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.
文摘Subjective: This study aimed to investigate the therapeutic mechanisms of 7-hydroxyflavone (7-HF) in treating myocardial ischemia/reperfusion injury (MI/RI) via network pharmacology, molecular docking, target validation, and experiments at the animal level. Methods: Firstly, the genes of 7-HF were acquired from PharmMapper, TCMSP, and SwissTargetPrediction. At the same time, MI/RI-related genes were obtained from OMIM, GeneCards, and TTD online platforms. Subsequently, string platform and Cytoscape 3.9.2 were used to construct protein-protein interaction network diagrams and 7-HF-targets-signaling pathways-MI/RI network. Then, the Metascape platform was used to conduct functional enrichment analyses. Next, AutoDock Vina and Pymol were used to perform molecular docking. The hub targets were validated in the GSE66360. Lastly, SOD, MDA, transmission electron microscope, quantitative real-time PCR, and western blot were used to validate in MI/RI rats. Results: 139 genes of 7-HF, 4832 genes of MI/RI were obtained. The 47 interact genes between 7-HF and MI/RI targets for MI/RI were likely to act through multiple pathways. And NQO1 was a critical target in the above process. In an animal experiment, 7-HF could relieve the injured interfibrillar mitochondria and myocardial fibers, decrease the expression of MDA and SOD, and increase the expression of Nrf2, NQO1 and HO-1 in the mRNA and protein level in the MI/RI rats. Conclusion: This study preliminarily demonstrated that 7-HF could provide cardioprotection by inhibiting the oxidative stress and up-regulating Nrf2/NQO1/HO-1 signaling pathway based on network pharmacology, molecular docking, target validation, and animal experiments.
基金Supported by Scientific Research Project of Guiyang College of Traditional Chinese Medicine[(2010)02]~~
文摘This study aimed to investigate the protective effects of zin-giberis and acniti praeparatae decoction on oxidative stress injury induced by my-ocardial ischemia reperfusion in rats. [Method] Myocardial ischemia-reperfusion was performed by ligation of the left anterior descending coronary artery for 30 min, fol-lowed by reperfusion for 60 min. The effects of zingiberis and acniti praeparatae decoction on ECG ST segment, myocardial infarction percentage, malondialdehyde （MDA） content in the serum, superoxide dismutase （SOD） activity and other indica-tors were observed. [Result] Zingiberis and acniti praeparatae decoction could effec-tively inhibit ECG ST segment elevation caused by myocardial ischemia-reperfusion injuries, reduce the percentage of myocardial infarction, decline the content of MDA in the serum, and increase the activity of SOD. [Conclusion] Zingiberis and acniti praeparatae decoction exhibits protective effects on oxidative injuries caused by my-ocardial ischemia-reperfusion injuries in rats, which may be involved in reducing the formation of myocardial free radicals and enhancing antioxidant capacity of my-ocardium.
基金supported by a grant from the Health and Family Planning Commission of Heilongjiang Province Research Project in China,No.2014-195the Education Department Science and Technology Foundation of Heilongjiang Province in China,No.12531741the Natural Science Foundation of Heilongjiang Province of China,No.H2015083
文摘Ligustrazine （2,3,5,6-tetramethylpyrazine） is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mecha- nism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administra- tion, and the most effective mode of administration for clinical treatment of cerebral ischemia/ reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine admin- istration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[（1,1-dimethylethyl）oxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC 195 after cerebral ischemia were better than ligustrazine.
文摘Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling pathway.This review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases.
基金the Scientific Foundation of Ministry of Health of China,No.98-2-283Shanghai Natural Science Foundation,No.98ZB14025
文摘AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expression and cell apoptosiswere detected in rat model of hepatic/ renalischemia-reperfusion injury.ELISA,immunohist-ochemistry and TUNEL were used.Someischemia-reperfusion rats were treated with anti-P-selectin mAb.RESULTS Hepatic/renal function insuffic-iency,up-regulated expression of P-selectin inplasma and hepatic/renal tissue,hepatic/renalhistopathological damages and cell apoptosiswere found in rats with hepatic/renal ischemia-reperfusion injury,while these changes becameless conspicuous in animals treated with anti-P-selectin mAb.CONCLUSION P-selectin might mediateneutrophil infiltration and cell apoptosis andcontribute to hepatic/renal ischemia-reperfusioninjury,anti-P-selectin mAb might be an efficientapproach for the prevention and treatment ofhepatic/renal ischemia-reperfusion injury.
文摘IM To observe the kinetics of D()lactate alteration in both portal and systemic circulations, and its relationship with intestinal injury in rats subjected to acute intestinal ischemiareperfusion.METHODS Anesthetized rats underwent 75min superior mesenteric artery occlusion followed by 6hour reperfusion. Plasma D()lactate levels were measured by an enzymatic spectrophotometric assay.RESULTS Intestinal ischemia for 75 min resulted in a significant elevation of D()lactate levels in portal vein as compared with the baseline values (P<005). Plasma D()lactate levels had a tendency to further increase after reperfusion up to 6 hours. Similar alterations in D()lactate were also found in systemic circulation, there were no significant differences between the portal and systemic circulations at any time point. Moreover, the macropathological evaluation scores were significantly correlated to the portal D()lactate levels in animals at various time points (r=0415, P<001). In addition,there was a remarkable rise of endotoxin concentration within the portal vein at the end of 75min ischemia (P<005), reaching a peak at 2 hours postreperfusion.CONCLUSION Acute intestinal ischemia is associated with failure of mucosal barrier resulting in increased plasma D()lactate levels in both portal and systemic blood. The subsequent reperfusion might further increase D()lactate levels, which are correlated to the macropathological alterations. Plasma D()lactate may be a useful marker of intestinal injury following both ischemia and reperfusion insults.
基金supported by Henan Province Natural Science Foundation(283v2110)
文摘Objective:To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury.Methods:A total of 48 male SD rats were randomly divided into control group(A),I/R group(B),high dose of rosiglitazone(C),low dose of rosiglitazone(D).Plasm concentration of creatine kinase(CK),CK-MB,hsCRP,Superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),nitric oxide(NO)and endothelin(ET)were measured 1 h later after I/R.24 h after I/R hearts were harvested to observe pathological and ultrastructural changes.Immunohistochemistry and western blotting was used to test CD40 expression in myocardial tissue.Area of myocardial infarction were tested,arrhythmia rate during I/R was recorded.Results:Plasm concentration of creatine kinase(CK),CK-MB,hsCRP,NO,MDA and ET were decreased in group C,D compared with group B.Plasm concentration of T-SOD and GSHPx was increased significantly in group C,D compared with group B.Compared with group B,pathological and ultrastructural changes in group C,D were slightly.Myocardial infarction area and arrhythmia rate were lower in group C,D compare with group B.Conclusions:Rosiglitazone can protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration,inhibit inflammatory reaction,improve endothelial function,reduce oxidative stress and calcium overload.
基金supported by Shanghai Natural Science Foundation(Grant No.14ZR1437200)Foundation of Medical Elite Personnel Training Program of Pudong New Area(Grant No.PWR12010-03)Key Disciplines and Specialties of Shanghai Pudong New Area(Grant No.PDZx2014-01)
文摘Objective:To study the protective effect of hyperoside(Hyp) on cardiac ischemia reperfusion injury and its potential mechanism.Methods:Rats were divided into two groups for the evaluation,the Hyp(50 uM Hyp;n=8) and the control group(n=8).Rat hearts were isolated and perfused with Krebs-Henseleit buffer(KHB) for 30 min.After being inhibited with cardioplegic solution,they were stored for 4 h in B21 solution at 4℃.Afterwards,rat hearts were perfused with KHB again for 45 min.In this period.Hyp was added into solutions of cardioplegia for storage and KHB.Parameters of cardiac functions,including heart rate,the systolic pressure of the left ventricle,the end-diastolic pressure of the left ventricle,the developed pressure of the left ventricle,the left-ventricular systolic pressure and the peak rise rate of the pressure of the left ventricle were recorded.The levels of adenosine triphosphate(ATP),the content of malondialdehyde and apoptotic cells were determined to evaluate the protective effect of Hyp on hearts suffered from ischemia reperfusion injury.Moreover,cultured cardiac myocytes were subjected to the process simulating ischemia/reperfusion.What were analyzed included the endoplasmic reticulum(ER) stress hallmarks expressions,such as binding immunoglobulin protein and C/EBP homologous protein,using the western blot and real-time PCR.Besides,the NF-E2-related factor 2(Nrf2) expression was measured to explore the potential mechanism.Results:Compared with the control group,the Hyp group had better cardiac functional parameters and higher ATP levels;pretreatment of Hyp greatly relieved the apoptosis of myocyte,decreased oxidative stress as well as ER stress and activated the signaling pathway of anti-oxidative Nrf2 to a further extent.Conclusions:Hyp plays an important role in preserving cardiac function by improving ATP levels of tissue,easing oxidative injury of myocardium and reducing apoptosis following IRI dramatically,while the ER stress inhibition and the downstream Nrf2 signaling activation may contribute to the effects of protection.
基金supported by a grant from the Jilin Provincial Science and Technology Development Program Foundation of China,No.20110915
文摘Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/ reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-de- pendently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reper- fusion injury. These findings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression.
