Background The protective effects against reperfusion injury of cardioprotective drugs have recently been evaluated and found to be inadequate. Guanxinshutong （GXST）, a combination of the traditional herb and Mongol...Background The protective effects against reperfusion injury of cardioprotective drugs have recently been evaluated and found to be inadequate. Guanxinshutong （GXST）, a combination of the traditional herb and Mongolian medicine, is effective and safe in treating angina pectoris in clinical trials. We assess the cardioprotective effects of GXST against myocardial ischemia and reperfusion （MI/R） injury in rats and explore its possible mechanism. Methods Forty-five male Sprague Dawley rats were randomized into three groups： non-MlfR group （Sham, n = 15）, MUR group treated with vehicle （Control, n = 15） and MI/R group treated with GXST （Drug, n = 15）. MI/R was induced by ligation of the left anterior descending coronary artery （LAD） for 30 minutes, followed by 2/24 hour reperfusion in the Control and Drug groups. In the Sham group, the LAD was exposed without occlusion. GXST powder （in the Drug group） or saline （in the Control and Sham groups） were administered via direct gastric gavage from 7 day prior to surgery. Blood samples were collected from the carotid artery （10 rats each group） after 2 hours of reperfusion, to determine the levels of tumor necrosis factor-or （TNF-ct）, interleukin-1 ~ （IL-113）, interleukin-6 （IL-6） and intercellular adhesion molecule-1 （ICAM-1） using enzyme-linked immunosorbent assays. The animals were then sacrificed and the hearts were harvested for histopathology and western blot analysis. Infarct size was measured in the remaining five rats in each group after 24 hours reperfusion. Results GXST significantly decreased levels of TNF-ct, IL-1β, IL-6, ICAM-1, apoptosis index （AI） and infarct size. GXST also obviously inhibited nuclear factor kappa B （NF.r,B） activity when compared with the Control group （all P 〈 0.05）. Conclusions GXST is effective in protecting the myocardium against MI/R injury in rats. Its possible cardioprotective mechanism involves inhibition of the inflammatory response and apoptosis following MI/R injury.展开更多
Background Electroacupuncture pretreatment plays a protective role in myocardial ischemia/reperfusion （I/R） injury and microRNAs （miRNAs） could act on various facets of cardiac function. However, the role of miRNA...Background Electroacupuncture pretreatment plays a protective role in myocardial ischemia/reperfusion （I/R） injury and microRNAs （miRNAs） could act on various facets of cardiac function. However, the role of miRNAs in the cardioprotection by electroacupuncture pre-treatment on myocardial I/R injury remains unknown. The purpose of the study was to examine whether miR-214 was involved in cardio-protection by electroacupuncture. Methods Using rat myocardial I/R model, we examined the role of electroacupuncture pretreatment in myocardial I/R injury and analyzed the changes in the expression of miR-214. In addition, I/R was simulated in vitro by performing oxy-gen-glucose deprivation （OGD） on H9c2 cell cultures, and the effect of electroacupuncture pretreatment on I/R injury as well as expressional level of miR-214 were examined in vitro. Furthermore, the miR-214 mimic was transfected into OGD-treated H9c2 cells, we analyzed the cell apoptosis, lactate dehydrogenase （LDH） and creatine kinase （CK） activities, intracellular free Ca2＋concentration （[Ca2＋]i） as well as the relative protein levels of sodium/calcium exchanger 1（NCX1）, BCL2-like 11 （BIM）, calmodulin-dependent protein kinase IIδ（CaMKIIδ） and Cyclophilin D （CypD）. Results The in vivo results revealed that compared with the I/R group, the electroacupuncture pretreatment group showed significant decreased myocardial infarct size, as well as the increased indices of the cardiac function, including heart rate, mean arterial pressure, left ventricular systolic pressure and maximal rate for left ventricular pressure rising and declining （±dp/dt max）. In addition, electroacupuncture pretreatment could inhibit the elevation of LDH and CK activities induced by I/R injury. The quantitative PCR （qPCR） results demonstrated electroacupuncture pretreatment could provide cardioprotection against myocardial I/R injury in rats with miR-214 up-regulation. In the meanwhile, in vitro, electroacupuncture pretreatment protected H9c2 cells from OGD-induced injury. Trans-fection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca2＋and down-regulating elevated protein levels of NCX1, BIM, CaMKIIδand CypD. Conclusions Our findings firstly demonstrated that electroacupuncture pretreatment promotes the expression of miR-214 in myocardial I/R injury and miR-214 contributes to the protective effect of electroacupuncture on myocardial I/R injury.展开更多
文摘Background The protective effects against reperfusion injury of cardioprotective drugs have recently been evaluated and found to be inadequate. Guanxinshutong （GXST）, a combination of the traditional herb and Mongolian medicine, is effective and safe in treating angina pectoris in clinical trials. We assess the cardioprotective effects of GXST against myocardial ischemia and reperfusion （MI/R） injury in rats and explore its possible mechanism. Methods Forty-five male Sprague Dawley rats were randomized into three groups： non-MlfR group （Sham, n = 15）, MUR group treated with vehicle （Control, n = 15） and MI/R group treated with GXST （Drug, n = 15）. MI/R was induced by ligation of the left anterior descending coronary artery （LAD） for 30 minutes, followed by 2/24 hour reperfusion in the Control and Drug groups. In the Sham group, the LAD was exposed without occlusion. GXST powder （in the Drug group） or saline （in the Control and Sham groups） were administered via direct gastric gavage from 7 day prior to surgery. Blood samples were collected from the carotid artery （10 rats each group） after 2 hours of reperfusion, to determine the levels of tumor necrosis factor-or （TNF-ct）, interleukin-1 ~ （IL-113）, interleukin-6 （IL-6） and intercellular adhesion molecule-1 （ICAM-1） using enzyme-linked immunosorbent assays. The animals were then sacrificed and the hearts were harvested for histopathology and western blot analysis. Infarct size was measured in the remaining five rats in each group after 24 hours reperfusion. Results GXST significantly decreased levels of TNF-ct, IL-1β, IL-6, ICAM-1, apoptosis index （AI） and infarct size. GXST also obviously inhibited nuclear factor kappa B （NF.r,B） activity when compared with the Control group （all P 〈 0.05）. Conclusions GXST is effective in protecting the myocardium against MI/R injury in rats. Its possible cardioprotective mechanism involves inhibition of the inflammatory response and apoptosis following MI/R injury.
基金This study was supported by a grant from the Hainan Provincial Nature Science Foundation
文摘Background Electroacupuncture pretreatment plays a protective role in myocardial ischemia/reperfusion （I/R） injury and microRNAs （miRNAs） could act on various facets of cardiac function. However, the role of miRNAs in the cardioprotection by electroacupuncture pre-treatment on myocardial I/R injury remains unknown. The purpose of the study was to examine whether miR-214 was involved in cardio-protection by electroacupuncture. Methods Using rat myocardial I/R model, we examined the role of electroacupuncture pretreatment in myocardial I/R injury and analyzed the changes in the expression of miR-214. In addition, I/R was simulated in vitro by performing oxy-gen-glucose deprivation （OGD） on H9c2 cell cultures, and the effect of electroacupuncture pretreatment on I/R injury as well as expressional level of miR-214 were examined in vitro. Furthermore, the miR-214 mimic was transfected into OGD-treated H9c2 cells, we analyzed the cell apoptosis, lactate dehydrogenase （LDH） and creatine kinase （CK） activities, intracellular free Ca2＋concentration （[Ca2＋]i） as well as the relative protein levels of sodium/calcium exchanger 1（NCX1）, BCL2-like 11 （BIM）, calmodulin-dependent protein kinase IIδ（CaMKIIδ） and Cyclophilin D （CypD）. Results The in vivo results revealed that compared with the I/R group, the electroacupuncture pretreatment group showed significant decreased myocardial infarct size, as well as the increased indices of the cardiac function, including heart rate, mean arterial pressure, left ventricular systolic pressure and maximal rate for left ventricular pressure rising and declining （±dp/dt max）. In addition, electroacupuncture pretreatment could inhibit the elevation of LDH and CK activities induced by I/R injury. The quantitative PCR （qPCR） results demonstrated electroacupuncture pretreatment could provide cardioprotection against myocardial I/R injury in rats with miR-214 up-regulation. In the meanwhile, in vitro, electroacupuncture pretreatment protected H9c2 cells from OGD-induced injury. Trans-fection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca2＋and down-regulating elevated protein levels of NCX1, BIM, CaMKIIδand CypD. Conclusions Our findings firstly demonstrated that electroacupuncture pretreatment promotes the expression of miR-214 in myocardial I/R injury and miR-214 contributes to the protective effect of electroacupuncture on myocardial I/R injury.
