【摘要】 目的:探讨血管紧张素转换酶抑制剂(ACEI)卡托普利(Cap)对钙激活中性蛋白酶(Calpain)介导的糖尿病大鼠心肌细胞凋亡及心功能的影响。方法:成年雄性SD大鼠30只,随机分为3组(n=10):正常对照组(NC组)、糖尿病组(DM组)、卡托普利治疗组(Cap组)。应用链脲佐菌素(STZ)诱导构建糖尿病大鼠模型,Cap组每日给予卡托普利(50 mg/kg)灌胃,其余两组给予等体积生理盐水。用药12周后,测量左心室收缩压(LVSP)、左心室舒张末期压力(LVDEP)、左心室内压最大上升速率(+dp/dtmax)和左心室内压最大下降速率(-dp/dtmax),蛋白印迹法检测心肌Calpain-1、Calpain-2、Bc-l 2、Bax、总Caspase3蛋白的表达,原位末端标记法检测计算心肌细胞凋亡指数(AI)。结果:与NC组相比,DM组大鼠LVDEP明显升高,LVSP、+dp/dtmax、-dp/dtmax明显降低(P<0.05);Bc-l 2蛋白表达减少,Calpain-1、Calpain-2、Bax、总Caspase3蛋白表达增加,AI明显增加(P<0.05);与DM组相比,Cap组大鼠LVDEP明显降低,LVSP、+dp/dtmax、-dp/dtmax明显升高(P<0.05);Bc-l 2蛋白表达增加,Calpain-1、Calpain-2、Bax、总Caspase3蛋白表达减少,AI明显减少(P<0.05)。结论:卡托普利可能通过抑制Calpain-1、Calpain-2的激活,上调Bc-l 2表达,下调Bax蛋白表达,减少Caspase3依赖性的心肌细胞凋亡,从而改善糖尿病大鼠心室功能和心肌结构。更多还原

【Abstract】 Objective: To investigate the effects of angiotensin converting enzyme inhibitor(ACEI) captopril on Calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats.Methods: Thirty adult male SD rats were randomly divided into 3 groups(n=10),normal control group(NC group),diabetes mellitus group(DM group)and captopril treated group(Cap group).Streptozocin(STZ) were used to make the model of diabetes mellitus,captopril was administrated by gavage at the dose of 50 mg/kg every day,while in NC group and DM group the same volume of normal saline was administrated.Twelve weeks later,left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVDEP),maximal rise rate of left ventricular pressure(+dp/dtmax) and maximal fall rate of left ventricular pressure(-dp/dtmax) were detected;Western blot was used to detect the expression of Calpain-1、Calpain-2、Bcl-2、Bax and total Caspase3 protein;apoptosis index(AI) were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL).Results: Compared with NC group,LVDEP was significantly higher;LVSP,+dp/dtmax and-dp/dtmax were significantly decreased(P<0.05);Bcl-2 protein expression was decreased;the expression of Calpain-1,Calpain-2,Bax and total Caspase3 protein were increased;the value of AI was significantly increased.Compared with DM group,LVDEP was significantly lower;LVSP,+dp/dtmax and-dp/dtmax were significantly increased(P<0.05);Bcl-2 protein expression was increased,the expression of Calpain-1,Calpain-2,Bax and total Caspase3 protein were decreased;the value of AI was significantly decreased(P<0.05).Conclusion: Captopril can protect diabetic myocardial structure through inhibiting activation of Calpain-1 and Calpain-2,up-regulating the expression of Bcl-2,down-regulating the expression of Bax to inhibit Caspase3 dependent apoptosis,thereby improving the ventricular function and myocardial structure.更多还原