卡托普利对糖尿病大鼠心肌细胞凋亡及相关蛋白表达的影响

目的:探讨血管紧张素转换酶抑制剂(ACEI)卡托普利对糖尿病(DM)大鼠心肌细胞凋亡及凋亡相关蛋白Bcl-2、Bax、Caspase-3表达的影响。方法:成年雄性SD大鼠30只,随机分为正常对照组(NC组)、DM组、卡托普利治疗组(Cap组),每组10只。应用链脲佐菌素(STZ)诱导构建DM大鼠模型,Cap组每日灌胃给予卡托普利50 mg/kg,其余两组给予等容积的0.9%氯化钠溶液。用药12周后,原位缺口末端标记法(TUNEL法)检测计算心肌细胞凋亡指数(AI),Western blot法检测心肌Bcl-2、Bax、Caspase-3蛋白的表达,透射电镜观察心肌超微结构变化。给药期间动态观察测定大鼠行为、体质量及血糖水平的改变。结果:与NC组相比,DM组大鼠心肌细胞AI明显升高,Bcl-2蛋白表达减少,Bax、Caspase-3蛋白表达增加;电镜示心肌细胞超微结构呈明显损伤性变化。与DM组相比,Cap组心肌细胞AI明显降低,Bcl-2蛋白表达增加,Bax、Caspase-3蛋白表达减少;超微结构损伤不同程度减轻。结论:卡托普利可能通过上调Bcl-2表达,下调Bax表达,减少Caspase-3依赖性的心肌细胞凋亡,从而起到保护DM大鼠心肌细胞的作用。

Effects of captopri1 on cardiomyocytes apoptosis and expression of apoptosis related proteins in diabetic rats

Objective: To Probe the effects of angiotensin converting enzyme inhibitor(ACEI) captopril on cardiomyocytes apoptosis and expression of apoptosis related proteins such as Bcl-2,Bax and Caspase-3 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).STZ were used to establish the model of diabetes mellitus,captopril was administrated through gavage at the dose of 50 mg/kg every day,while the same volume of normal saline was administrated in NC group and DM group.Twelve weeks later,the apoptotic index(AI) of cardiomyocytes was detected by terminal deoxynuleotidyl transferase mediated dUTP nick end abeling(TUNEL),the protein expressions of Bcl-2,Bax and Caspase-3 were measured with Western blot,the myocardial ultrastructural changes were observed under transmission electron microscopy,and the rats’weight and blood glucose levels were monitored dynamically during the 12 weeks.Results: Compared with NC group,the value of AI was significantly increased,the expression of Bcl-2 protein was decreased,the expressions of Bax and Caspase-3 were increased,transmission electron microscope showed serious ultrastruc-ture injury in DM group.Compared with DM group,the value of AI was significantly decreased,the expression of Bcl-2 protein was increased,the expression of Bax and Caspase-3 was decreased,light ultrastructure morphological injury was found in Cap group.Conclusion: Captopril can protect diabetic cardiomyocytes through up-regulating the expres-sion of Bcl-2,down-regulating the expression of Bax to inhibit Caspase-3 dependent apoptosis.