【摘要】 目的观察二氮嗪对缺血-再灌流心肌细胞凋亡,以及对Bax、Bcl-2和Caspase-3表达的影响。方法21只SD大鼠随机分为假手术组(sham operation,SO),缺血-再灌流组(ischemia/reperfusion,IR)和二氮嗪处理组(Diazoxide,DI)。SO组和IR组静脉注射相应量溶媒,DI组12.5 mg/kg剂量静脉注射二氮嗪。10min后SO组不结扎前降支,4 h后取心脏,而IR组和DI组结扎前降支2 h,再灌流2 h。采用TUNEL法和免疫组化法检测缺血心肌细胞凋亡和Bax、Bcl-2、Caspase-3表达,及心肌梗死范围。结果与SO组相比,IR和DI组心肌细胞凋亡率显著增加(P<0.05),Bax、Bcl-2和Caspase-3蛋白阳性细胞指数明显升高(P<0.05);与IR组相比,DI组明显降低心肌细胞凋亡率(P<0.05)和Bax,Caspase-3蛋白阳性细胞指数(P<0.05),增加Bcl-2蛋白阳性细胞指数(P<0.05)。IR组心肌梗死范围为(36.9±2.3)%,DI组为(20.0±8)%,两组差异有显著性(P<0.05)。结论二氮嗪通过上调Bcl-2表达,下调Bax及Caspase-3表达而减少在体大鼠缺血-再灌流损伤心肌细胞凋亡。更多还原

【Abstract】 Objective To investigate the effect of diazoxide on apoptosis induced by myocardial ischemia/reperfusion injury of rats and the expression of Bax,Bcl-2 and Caspase-3 proteins.Methods Twenty-one healthy SD rats were randomly divided into three groups: sham-operated group,ischemia/reperfusion group and diazoxide treatment group.The diazoxide group received diazoxide at 12.5 mg/kg through the right femoral vein.The sham-operated group and ischemia/reperfusion group were only given with the same amount of soluent.After 10 minutes,a left thoracotomy was performed and the left anterior descending branch was ligated for 2 hours in ischemia/reperfusion group and diazoxide treatment group.The sham-operated group was had thoracotomy only.2 hours later,the left anterior descending branch was reperfused.The reperfusion was continued for 2 hours and then the heart was quickly removed to be used for measurement of the apoptosis rate by TUNEL and the expression of Bax,Bcl-2 and Caspase-3 proteins in ischemic myocytes by immunohisto chemistry.Results Compared with sham-operated group,the apoptosis and the positive cell index(PCI) of Bax,Bcl-2 and Caspase-3 proteins in ischemia/reperfusion group and diazoxide group was greatly increased(P<0.05).Compared with ischemia/reperfusion group,the apoptosis rate and the PCI of Bax and Caspase-3 proteins in diazoxide group was significantly decreased(P<0.05),while the PCI of Bcl-2 protein was greatly increased(P<0.05).The infarct size was(36.9±2.3) % in IR group while diazoxide reduced the infarct size to(20.0±8)%(P<0.05).Conclusion These results indicated that diazoxide could reduce infarct size and decrease apoptosis induced by myocardial ischemia/reperfusion injury in rats by upregulating the expression of Bcl-2 protein and inhibiting the expression of Bax and Caspase3 proteins.更多还原