几种ACEI对实验性糖尿病大鼠心肌细胞凋亡和Caspase-3及Fas、FasL基因表达影响的类效应

目的:探讨几种血管紧张素转换酶抑制剂(ACEI)卡托普利、培哚普利、咪达普利、贝那普利、福辛普利对糖尿病大鼠左室心功能及心肌细胞凋亡和凋亡相关蛋白影响的类效应。方法:将48只SD大鼠腹腔注射链脲佐菌素(STZ)诱发糖尿病模型,随机分为5个给药组和1个糖尿病组(每组8只),另选8只做正常对照组。给药组每日分别灌胃给予卡托普利(50 mg/kg),培哚普利(雅施达4 mg/kg),咪达普利(达爽10 mg/kg),贝那普利(洛汀新10 mg/kg),福辛普利(蒙诺10 mg/kg),糖尿病组给予生理盐水灌胃,共8周。对照观察心肌细胞凋亡、心肌组织Fas、FasL蛋白、Caspase-3及其Fas mRNA表达的变化。结果:与正常对照组相比,糖尿病给药组及未给药组的心肌细胞凋亡指数明显增高(均为P<0.05);Caspase-3阳性蛋白表达率明显增高(均为P<0.05);Fas蛋白阳性染色指数增高(均为P<0.05);Fas的mRNA表达明显增高(均为P<0.05)。但糖尿病给药组的较未给药组低(均为P<0.05)。所有各组的FasL蛋白阳性染色指数差异不明显(均为P>0.05)。各种ACEI治疗组之间差异无显著性(均为P>0.05)。结论:糖尿病心肌病的发生、发展过程中有心肌细胞凋亡的变化和Caspase家族及Fas、FasL系统的参与;糖尿病大鼠心肌细胞凋亡指数、心肌组织Fas蛋白以及Fas的mRNA表达水平、Caspase-3蛋白表达水平增高。ACEI干预糖尿病心肌病,能够降低细胞凋亡及Fas基因的表达及Caspase-3蛋白表达水平,且几种ACEI具有类效应。

Class Effects of Several ACEIs on Cadiocyte Apoptosis and Expression of Caspase-3 and Fas/FasL Genes in Experimental Diabetic Rats

Objective:To study the class effects of different kinds of angiotensin-converting enzyme inhibitor(ACEI) such as captopril,perindopril,imidapril,benazepril and fosinopril on cardiomyocytes apoptosis and expression of caspase3 and Fas/FasL genes of cardiomyocytes in experimental diabetic rats.Methods:A total of 48 SD rats models with diabetes were established by intraperitoneal injection of STZ,and then were divided into one diabetes group and five treatment groups according to different kinds of ACEIs as 50 mg/kg captopril,50 mg/kg perindopril,10 mg/kg imidapril,50 mg/kg benazepril and 50 mg/kg fosinopril respectively.Another 8 healthy rats were set as control group.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) and ABC immunohistochemical staining were used respectively to detect the changes of apoptosis and protein expression of caspase-3,Fas and FasL genes,and mRNA expression of Fas gene was evaluated by RT-PCR analysis.Results:Compared with the control group,the apoptosis index was higher in the diabetic groups with or without treatment(all P<0.05);and the levels of expression of caspase-3,Fas and Fas mRNA were higher too(all P<0.05).But compared with those in the diabetic model group,the above results were lower in the treated groups(all P<0.05).However,there was not significant difference among the groups that were given different ACEI(P>0.05).Conclusion:The mentioned parameters suggest that caspase-3 and Fas/FasL systems are involved in the onsets and development of diabetic cardiomyopathy.ACEI administration in case of diabetic cardiomypathy may decrease the expression of caspase-3 and Fas and FasL genes,and different ACEIs have class effects.