Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell i...Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and thrombosis.These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and platelets.In clinical practice,aside from drugs that target abnormal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances.Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory disturbances.In recent years,numerous research papers on the improvement of microcirculatory function by natural products have been published in international journals.In 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology&Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine,respectively.This review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPSinduced microcirculatory disturbances and tissue injury.Based on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.展开更多
AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated...AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused （10 mg/kg per hour） from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （RBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by immunofluorescence.RESULTS： After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.展开更多
Acute brain injury caused by subarachnoid hemorrhage is the major cause of poor prognosis. The pathology of subarachnoid hemorrhage likely involves major morphological changes in the microcirculation. However, previou...Acute brain injury caused by subarachnoid hemorrhage is the major cause of poor prognosis. The pathology of subarachnoid hemorrhage likely involves major morphological changes in the microcirculation. However, previous studies primarily used fixed tissue or delayed injury models. Therefore, in the present study, we used in vivo imaging to observe the dynamic changes in cerebral microcirculation after subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by perforation of the bifurcation of the middle cerebral and anterior cerebral arteries in male C57/BL6 mice. The diameter of pial arterioles and venules was measured by in vivo fluorescence microscopy at different time points within 180 minutes after subarachnoid hemorrhage. Cerebral blood flow was examined and leukocyte adhesion/albumin extravasation was determined at different time points before and after subarachnoid hemorrhage. Cerebral pial microcirculation was abnormal and cerebral blood flow was reduced after subarachnoid hemorrhage. Acute vasoconstriction occurred predominantly in the arterioles instead of the venules. A progressive increase in the number of adherent leukocytes in venules and substantial albumin extravasation were observed between 10 and 180 minutes after subarachnoid hemorrhage. These results show that major changes in microcirculation occur in the early stage of subarachnoid hemorrhage. Our findings may promote the development of novel therapeutic strategies for the early treatment of subarachnoid hemorrhage.展开更多
AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 eac...AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 each):Sham group and I/R group(infused with saline),TSA group,TSA + I/R group and I/R + TSA group(infused with TSA,5 mg/kg per hour).Mesenteric I/R were conducted by a ligation of the mesenteric artery and vein(10 min) and subsequent release of the occlusion.TSA was continuously infused either starting from 10 min before the ischemia or 10 min after reperfusion.Changes in mesenteric microcirculatory variables,including diameter of venule,velocity of red blood cells in venule,leukocyte adhesion,free radicals released from venule,albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope.Meanwhile,the expression of adhesion molecules CD11b/CD18 on neutrophils was evaluated by flow cytometry.Ultrastructural evidence of mesenteric venules damage was assessed after microcirculation observation.RESULTS:I/R led to multiple responses in mesenteric post-capillary venules,including a significant increase in the adhesion of leukocytes,production of oxygen radicals in the venular wall,albumin efflux and enhanced mast cell degranulation in vivo.All the I/R-induced manifestations were significantly reduced by pre-or post-treatment with TSA,with the exception that the I/R-induced increase in mast cell degranulation was inhibited only by pre-treatment with TSA.Moreover,preor post-treatment with TSA significantly attenuated the expression of CD11b/CD18 on neutrophils,reducing the increase in the number of caveolae in the endothelial cells of mesentery post-capillary venules induced by I/R.CONCLUSION:The results demonstrated that TSA protects from and ameliorates the microcirculation disturbance induced by I/R,which was associated with TSA inhibiting the production of oxygen-free radicals in the venular wall and the expression of CD11b/CD18 on neutrophils.展开更多
AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope ...AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation,such as diameters of arterioles and venules,velocity of RBCs in venules,leukocyte rolling,adhesion and emigration,free radicals released from post-capillary venules,FITC- albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile,the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils,and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation,including a significant increase in the positive region of venulestained with Monastral blue B,rolling and adhesion of leukocytes,production of oxygen radical in venular wall,albumin efflux and enhanced mast cell degranulation in vivo,all of which,except for the leukocyte rolling,were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils,and the expression of ICAM-1 in HUVECs were increased by exposure to LPS,and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.展开更多
The adipose tissue of mammals represents an important energy-storing and endocrine organ, and its dysfunction is relevant to the onset of several health problems, including non-alcoholic fatty liver disease (NAFLD). H...The adipose tissue of mammals represents an important energy-storing and endocrine organ, and its dysfunction is relevant to the onset of several health problems, including non-alcoholic fatty liver disease (NAFLD). However, whether treatments targeting adipose dysfunction could alleviate NAFLD has not been well-studied. Adrenomedullin 2 (ADM2), belonging to the CGRP superfamily, is a protective peptide that has been shown to inhibit adipose dysfunction. To investigate the adipose tissue-specific effects of ADM2 on NAFLD, adipose-specific ADM2-overexpressing transgenic (aADM2-tg) mice were developed. When fed a high-fat diet, aADM2-tg mice displayed decreased hepatic triglyceride accumulation compared to wild-type mice, which was attributable to the inhibition of hepatic de novo lipogenesis. Results from lipidomics studies showed that ADM2 decreased ceramide levels in adipocytes through the upregulation of ACER2, which catalyzes ceramide catabolism. Mechanically, activation of adipocyte HIF2α was required for ADM2 to promote ACER2-dependent adipose ceramide catabolism as well as to decrease hepatic lipid accumulation. This study highlights the role of ADM2 and adipose-derived ceramide in NAFLD and suggests that its therapeutic targeting could alleviate disease symptoms.展开更多
Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global pu...Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound Tem preparation, Chinese materia medica, and active components on I/R-induced cerebral imicrocirculatory disturbances, brain injury and neuron damage. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. Alt rights reserved.展开更多
Acute coronary syndrome, stroke and other ischemic events continue to be the most common causes of mortality and morbidity in the world, and their incidence is rapidly increasing in the developing nations. These cardi...Acute coronary syndrome, stroke and other ischemic events continue to be the most common causes of mortality and morbidity in the world, and their incidence is rapidly increasing in the developing nations. These cardiovascular disorders clinically manifest as acute atherothrombotic events. Application of oral antiplatelet drugs is a milestone in the therapy of cardiovascular diseases. However, the limited efficacy of these drugs in the setting of arterial thrombosis, their unfavorable side effects, cost-to-benefit issues and the drug resistance phenomenon substantiate the need for the development of new and more efficacious antithrombotic drugs. In recent years, with the progress in the study of the Chinese medicine pharmacology, many Chinese herbs and formulas, as well as active constituents have been reported to possess not only effects on platelet aggregation and activation but also beneficial roles in vascular functions. Compared with currently used antithrombotic agents, herb remedies exert antithrombotic effects in a multi-pathway and multi-target manner. This paper will cover the progress in research on the ameliorating effects of herbal remedies on thrombosis, with focusing on their protection of vascular endothelial cells and inhibition of platelet activation.展开更多
Objective: To investigate the effect of paeonol on lipopolysaccheride(LPS)-induced rat mesenteric microcirculatory dysfunctions.Methods: Male Wistar rats were randomly distributed into 5 groups(n=6 in each): Sham grou...Objective: To investigate the effect of paeonol on lipopolysaccheride(LPS)-induced rat mesenteric microcirculatory dysfunctions.Methods: Male Wistar rats were randomly distributed into 5 groups(n=6 in each): Sham group, LPS group, paeonol group, paeonol+LPS group, and LPS+paeonol group. Endotoximia model was conducted by continuous LPS infusion. Changes in mesenteric microcirculatory variables, including diameter of venule, velocity of red blood cells in venule, leukocyte adhesion, free radicals produced in venule and albumin leakage from venule, were observed through an inverted intravital microscope. Meanwhile, the expression of myeloperoxidase(MPO), CD18,intercellular adhesion molecule-1(ICAM-1), toll-like receptor 4(TLR4), nuclear factor-kappa B p65 subunit(NF-κB p65), activator protein-1(AP-1), and Jun N-terminal kinase(JNK) was assessed by Western blot.Results: After infusion of LPS, the number of leukocytes adherent to venular wall, the intensity of dihydrorhodamine 123(DHR)fluorescence in the venular walls, and albumin leakage from venules were significantly increased, whereas the red blood cell velocity in venule was decreased. All the manifestations were significantly reduced by pre-treatment and post-treatment with paeonol. Moreover, paeonol significantly attenuated the expression of MPO, CD18, ICAM-1, TLR4, NF-κB p65, AP-1 and JNK in rat mesentery after LPS.Conclusions: The results demonstrated that paeonol could protect from and ameliorate the microcirculation disturbance induced by LPS.展开更多
Purpose： To investigate the effects of salvianolic acid B （SAB） on tumor necrosis factor a （TNF-a） induced alterations of cerebral microcirculation with a bone-abrading model. Methods： The influences of cranioto...Purpose： To investigate the effects of salvianolic acid B （SAB） on tumor necrosis factor a （TNF-a） induced alterations of cerebral microcirculation with a bone-abrading model. Methods： The influences of craniotomy model and bone-abrading model on cerebral microcirculation were compared. The bone-abrading method was used to detect the effects of intracerebroventricular application of 40 μg/kg.bw TNF-a on cerebral venular leakage of fluorescein isothiocyanate （FITC）- albulmin and the rolling and adhesion of leukocytes on venules with fluorescence tracer rhodamine 6G, The therapeutical effects of SAB on TNF-a induced microcirculatory alteration were observed, with continuous intravenous injection of 5 mg/kg.h SAB starting at 20 min before or 20 min after TNF-a administration, respectively, The expressions of CDllb/CD18 and CD62L in leukocytes were measured with flow cytometry, Immunohistochemical staining was also used to detect E-selectin and ICAM-1 expression in endothelial cells, Results： Compared with craniotomy method, the bone-abrading method preserved a higher erythrocyte velocity in cerebral venules and more opening capillaries. TNF-a intervention only caused responses of vascular hyperpermeability and leukocyte roiling on venular walls, without leukocyte adhesion and other hemodynamic changes. Pre- or post-SAB treatment attenuated those responses and suppressed the enhanced expressions of CDII b/CDI8 and CD62L in leukocytes and E-selectin and ICAM-I in endothelial cells induced by TNF-a. Conclusions： The pre- and post-applications of SAB during TNF-a stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling.展开更多
Lipopolysaccharide(LPS)-induced endotoxemia is a critical condition that initiates microcirculatory disturbance and may progress to multiple organ failure that threatens the lives of millions of people around the worl...Lipopolysaccharide(LPS)-induced endotoxemia is a critical condition that initiates microcirculatory disturbance and may progress to multiple organ failure that threatens the lives of millions of people around the world each year.The pathology of endotoxemia involves multiple insults mediated by a range of signaling pathways.Multitarget management is required to relieve endotoxemia.Traditional Chinese medicine(TCM)is a type of therapeutic that commonly contains numerous components and,thus,exhibits multitarget potential.More importantly,some TCM formulas have been proposed and used for effective treatment of endotoxemia-like diseases.In the past 20 years,an increasing number of studies have explored the effects and mechanisms of these formulas and their major bioactive components on microcirculatory disturbance and organ injury caused by LPS.The results obtained thus far provide support for the clinical use of TCM and shed light on the underlying mechanisms.展开更多
Objective: To investigate the effect of Panax notoginseng saponins(PNS) on ischemia reperfusion(I/R) induced rat mesenteric microcirculatory dysfunctions.Methods: Male Wistar rats weighting 200–250 g were subjected t...Objective: To investigate the effect of Panax notoginseng saponins(PNS) on ischemia reperfusion(I/R) induced rat mesenteric microcirculatory dysfunctions.Methods: Male Wistar rats weighting 200–250 g were subjected to 10 min ligation of the superior mesenteric artery and vein, followed by60 min reperfusion. PNS(5 mg/kg/hr) was continuously administrated starting from 10 min before ischemia or 10 min after reperfusion until60 min after reperfusion via left jugular vein. Leukocytes adhesion, mast cell degranulation, endothelial peroxidation, and albumin leakage of rat mesenteric venules were observed. Serum myeloperoxidase(MPO) level, intercellular adhesion molecule-1(ICAM-1) expression and Src phosphorylation were examined.Results: PNS ameliorated leukocyte adhesion and mast cell degranulation, while with no obvious effects on endothelial peroxidation and albumin leakage. In addition, PNS inhibited serum MPO increase, intestinal ICAM-1 expression and Src phosphorylation induced by I/R.Conclusions: PNS ameliorated I/R-induced leukocyte adhesion and mast cell degranulation, the former is related to its inhibition of Src phosphorylation and ICAM-1 expression.展开更多
Cardiotonic Pills(CP)is a compound preparation of Chinese medicine consisting of Salvia miltiorrhiza,Panax notoginseng and Borneol,and it has been approved in 1994by the China State Food and Drug Administration for tr...Cardiotonic Pills(CP)is a compound preparation of Chinese medicine consisting of Salvia miltiorrhiza,Panax notoginseng and Borneol,and it has been approved in 1994by the China State Food and Drug Administration for treating ischemic angina pectoris.It has passed the Phase II clinical trials by the US Food and Drug Administration in2009,December,demonstrating its potential to prolong展开更多
On behalf of the editorial team of World Journal of Traditional Chinese Medicine(WJTCM),we would like to convey our sincere gratitude to the great efforts of our editorial board members,referees,authors,readers and al...On behalf of the editorial team of World Journal of Traditional Chinese Medicine(WJTCM),we would like to convey our sincere gratitude to the great efforts of our editorial board members,referees,authors,readers and all the warmhearted supporters to contribute for the journal growth in the first year of its release in 2015.展开更多
基金supported by the National Natural Science Foundation of China(81873217 and 82074310)the State Key Laboratory of Core Technology in Innovative Chinese Medicine(20221108).
文摘Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and thrombosis.These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and platelets.In clinical practice,aside from drugs that target abnormal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances.Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory disturbances.In recent years,numerous research papers on the improvement of microcirculatory function by natural products have been published in international journals.In 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology&Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine,respectively.This review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPSinduced microcirculatory disturbances and tissue injury.Based on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.
基金Supported by Tianjin Tasly Group, Tianjin, China
文摘AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused （10 mg/kg per hour） from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （RBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by immunofluorescence.RESULTS： After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.
基金supported by the National Natural Science Foundation of China,No.81100856
文摘Acute brain injury caused by subarachnoid hemorrhage is the major cause of poor prognosis. The pathology of subarachnoid hemorrhage likely involves major morphological changes in the microcirculation. However, previous studies primarily used fixed tissue or delayed injury models. Therefore, in the present study, we used in vivo imaging to observe the dynamic changes in cerebral microcirculation after subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by perforation of the bifurcation of the middle cerebral and anterior cerebral arteries in male C57/BL6 mice. The diameter of pial arterioles and venules was measured by in vivo fluorescence microscopy at different time points within 180 minutes after subarachnoid hemorrhage. Cerebral blood flow was examined and leukocyte adhesion/albumin extravasation was determined at different time points before and after subarachnoid hemorrhage. Cerebral pial microcirculation was abnormal and cerebral blood flow was reduced after subarachnoid hemorrhage. Acute vasoconstriction occurred predominantly in the arterioles instead of the venules. A progressive increase in the number of adherent leukocytes in venules and substantial albumin extravasation were observed between 10 and 180 minutes after subarachnoid hemorrhage. These results show that major changes in microcirculation occur in the early stage of subarachnoid hemorrhage. Our findings may promote the development of novel therapeutic strategies for the early treatment of subarachnoid hemorrhage.
基金Supported by Production of New Medicine Program of Ministry of Science and Technology of the People's Republic of China,No.2008ZX09401
文摘AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 each):Sham group and I/R group(infused with saline),TSA group,TSA + I/R group and I/R + TSA group(infused with TSA,5 mg/kg per hour).Mesenteric I/R were conducted by a ligation of the mesenteric artery and vein(10 min) and subsequent release of the occlusion.TSA was continuously infused either starting from 10 min before the ischemia or 10 min after reperfusion.Changes in mesenteric microcirculatory variables,including diameter of venule,velocity of red blood cells in venule,leukocyte adhesion,free radicals released from venule,albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope.Meanwhile,the expression of adhesion molecules CD11b/CD18 on neutrophils was evaluated by flow cytometry.Ultrastructural evidence of mesenteric venules damage was assessed after microcirculation observation.RESULTS:I/R led to multiple responses in mesenteric post-capillary venules,including a significant increase in the adhesion of leukocytes,production of oxygen radicals in the venular wall,albumin efflux and enhanced mast cell degranulation in vivo.All the I/R-induced manifestations were significantly reduced by pre-or post-treatment with TSA,with the exception that the I/R-induced increase in mast cell degranulation was inhibited only by pre-treatment with TSA.Moreover,preor post-treatment with TSA significantly attenuated the expression of CD11b/CD18 on neutrophils,reducing the increase in the number of caveolae in the endothelial cells of mesentery post-capillary venules induced by I/R.CONCLUSION:The results demonstrated that TSA protects from and ameliorates the microcirculation disturbance induced by I/R,which was associated with TSA inhibiting the production of oxygen-free radicals in the venular wall and the expression of CD11b/CD18 on neutrophils.
文摘AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation,such as diameters of arterioles and venules,velocity of RBCs in venules,leukocyte rolling,adhesion and emigration,free radicals released from post-capillary venules,FITC- albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile,the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils,and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation,including a significant increase in the positive region of venulestained with Monastral blue B,rolling and adhesion of leukocytes,production of oxygen radical in venular wall,albumin efflux and enhanced mast cell degranulation in vivo,all of which,except for the leukocyte rolling,were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils,and the expression of ICAM-1 in HUVECs were increased by exposure to LPS,and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.
基金National Key Research and Development Program of China(Nos.2020YFA0803801,2022YFA0806400,and 2018YFA0800701)National Natural Science Foundation of China(Nos.81921001 and 32200949)+1 种基金project funded by China Postdoctoral Science Foundation(BX20220021,China)Xin Du and Julian Heng(Remotely Consulting,Australia)provided professional English-language editing of this article(Certificate No.2Tv2Ry7I).
文摘The adipose tissue of mammals represents an important energy-storing and endocrine organ, and its dysfunction is relevant to the onset of several health problems, including non-alcoholic fatty liver disease (NAFLD). However, whether treatments targeting adipose dysfunction could alleviate NAFLD has not been well-studied. Adrenomedullin 2 (ADM2), belonging to the CGRP superfamily, is a protective peptide that has been shown to inhibit adipose dysfunction. To investigate the adipose tissue-specific effects of ADM2 on NAFLD, adipose-specific ADM2-overexpressing transgenic (aADM2-tg) mice were developed. When fed a high-fat diet, aADM2-tg mice displayed decreased hepatic triglyceride accumulation compared to wild-type mice, which was attributable to the inhibition of hepatic de novo lipogenesis. Results from lipidomics studies showed that ADM2 decreased ceramide levels in adipocytes through the upregulation of ACER2, which catalyzes ceramide catabolism. Mechanically, activation of adipocyte HIF2α was required for ADM2 to promote ACER2-dependent adipose ceramide catabolism as well as to decrease hepatic lipid accumulation. This study highlights the role of ADM2 and adipose-derived ceramide in NAFLD and suggests that its therapeutic targeting could alleviate disease symptoms.
文摘Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound Tem preparation, Chinese materia medica, and active components on I/R-induced cerebral imicrocirculatory disturbances, brain injury and neuron damage. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. Alt rights reserved.
文摘Acute coronary syndrome, stroke and other ischemic events continue to be the most common causes of mortality and morbidity in the world, and their incidence is rapidly increasing in the developing nations. These cardiovascular disorders clinically manifest as acute atherothrombotic events. Application of oral antiplatelet drugs is a milestone in the therapy of cardiovascular diseases. However, the limited efficacy of these drugs in the setting of arterial thrombosis, their unfavorable side effects, cost-to-benefit issues and the drug resistance phenomenon substantiate the need for the development of new and more efficacious antithrombotic drugs. In recent years, with the progress in the study of the Chinese medicine pharmacology, many Chinese herbs and formulas, as well as active constituents have been reported to possess not only effects on platelet aggregation and activation but also beneficial roles in vascular functions. Compared with currently used antithrombotic agents, herb remedies exert antithrombotic effects in a multi-pathway and multi-target manner. This paper will cover the progress in research on the ameliorating effects of herbal remedies on thrombosis, with focusing on their protection of vascular endothelial cells and inhibition of platelet activation.
基金supported by the Production of New Medicine Program of Ministry of Science and Technology of the People’s Republic of China(2008ZX09401)
文摘Objective: To investigate the effect of paeonol on lipopolysaccheride(LPS)-induced rat mesenteric microcirculatory dysfunctions.Methods: Male Wistar rats were randomly distributed into 5 groups(n=6 in each): Sham group, LPS group, paeonol group, paeonol+LPS group, and LPS+paeonol group. Endotoximia model was conducted by continuous LPS infusion. Changes in mesenteric microcirculatory variables, including diameter of venule, velocity of red blood cells in venule, leukocyte adhesion, free radicals produced in venule and albumin leakage from venule, were observed through an inverted intravital microscope. Meanwhile, the expression of myeloperoxidase(MPO), CD18,intercellular adhesion molecule-1(ICAM-1), toll-like receptor 4(TLR4), nuclear factor-kappa B p65 subunit(NF-κB p65), activator protein-1(AP-1), and Jun N-terminal kinase(JNK) was assessed by Western blot.Results: After infusion of LPS, the number of leukocytes adherent to venular wall, the intensity of dihydrorhodamine 123(DHR)fluorescence in the venular walls, and albumin leakage from venules were significantly increased, whereas the red blood cell velocity in venule was decreased. All the manifestations were significantly reduced by pre-treatment and post-treatment with paeonol. Moreover, paeonol significantly attenuated the expression of MPO, CD18, ICAM-1, TLR4, NF-κB p65, AP-1 and JNK in rat mesentery after LPS.Conclusions: The results demonstrated that paeonol could protect from and ameliorate the microcirculation disturbance induced by LPS.
基金This study was supported by the General Program from the Natural Science Foundation of China，Southern Medical University Research Program for Young Scientists Training
文摘Purpose： To investigate the effects of salvianolic acid B （SAB） on tumor necrosis factor a （TNF-a） induced alterations of cerebral microcirculation with a bone-abrading model. Methods： The influences of craniotomy model and bone-abrading model on cerebral microcirculation were compared. The bone-abrading method was used to detect the effects of intracerebroventricular application of 40 μg/kg.bw TNF-a on cerebral venular leakage of fluorescein isothiocyanate （FITC）- albulmin and the rolling and adhesion of leukocytes on venules with fluorescence tracer rhodamine 6G, The therapeutical effects of SAB on TNF-a induced microcirculatory alteration were observed, with continuous intravenous injection of 5 mg/kg.h SAB starting at 20 min before or 20 min after TNF-a administration, respectively, The expressions of CDllb/CD18 and CD62L in leukocytes were measured with flow cytometry, Immunohistochemical staining was also used to detect E-selectin and ICAM-1 expression in endothelial cells, Results： Compared with craniotomy method, the bone-abrading method preserved a higher erythrocyte velocity in cerebral venules and more opening capillaries. TNF-a intervention only caused responses of vascular hyperpermeability and leukocyte roiling on venular walls, without leukocyte adhesion and other hemodynamic changes. Pre- or post-SAB treatment attenuated those responses and suppressed the enhanced expressions of CDII b/CDI8 and CD62L in leukocytes and E-selectin and ICAM-I in endothelial cells induced by TNF-a. Conclusions： The pre- and post-applications of SAB during TNF-a stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling.
基金supported by the National Natural Science Foundation of China(No.81873217)。
文摘Lipopolysaccharide(LPS)-induced endotoxemia is a critical condition that initiates microcirculatory disturbance and may progress to multiple organ failure that threatens the lives of millions of people around the world each year.The pathology of endotoxemia involves multiple insults mediated by a range of signaling pathways.Multitarget management is required to relieve endotoxemia.Traditional Chinese medicine(TCM)is a type of therapeutic that commonly contains numerous components and,thus,exhibits multitarget potential.More importantly,some TCM formulas have been proposed and used for effective treatment of endotoxemia-like diseases.In the past 20 years,an increasing number of studies have explored the effects and mechanisms of these formulas and their major bioactive components on microcirculatory disturbance and organ injury caused by LPS.The results obtained thus far provide support for the clinical use of TCM and shed light on the underlying mechanisms.
基金supported by the Production of New Medicine Program of Ministry of the Science and Technology of the People’s Republic of China[2010ZX09401-406]
文摘Objective: To investigate the effect of Panax notoginseng saponins(PNS) on ischemia reperfusion(I/R) induced rat mesenteric microcirculatory dysfunctions.Methods: Male Wistar rats weighting 200–250 g were subjected to 10 min ligation of the superior mesenteric artery and vein, followed by60 min reperfusion. PNS(5 mg/kg/hr) was continuously administrated starting from 10 min before ischemia or 10 min after reperfusion until60 min after reperfusion via left jugular vein. Leukocytes adhesion, mast cell degranulation, endothelial peroxidation, and albumin leakage of rat mesenteric venules were observed. Serum myeloperoxidase(MPO) level, intercellular adhesion molecule-1(ICAM-1) expression and Src phosphorylation were examined.Results: PNS ameliorated leukocyte adhesion and mast cell degranulation, while with no obvious effects on endothelial peroxidation and albumin leakage. In addition, PNS inhibited serum MPO increase, intestinal ICAM-1 expression and Src phosphorylation induced by I/R.Conclusions: PNS ameliorated I/R-induced leukocyte adhesion and mast cell degranulation, the former is related to its inhibition of Src phosphorylation and ICAM-1 expression.
文摘Cardiotonic Pills(CP)is a compound preparation of Chinese medicine consisting of Salvia miltiorrhiza,Panax notoginseng and Borneol,and it has been approved in 1994by the China State Food and Drug Administration for treating ischemic angina pectoris.It has passed the Phase II clinical trials by the US Food and Drug Administration in2009,December,demonstrating its potential to prolong
文摘On behalf of the editorial team of World Journal of Traditional Chinese Medicine(WJTCM),we would like to convey our sincere gratitude to the great efforts of our editorial board members,referees,authors,readers and all the warmhearted supporters to contribute for the journal growth in the first year of its release in 2015.
