曲美他嗪与雷米普利对心力衰竭大鼠心肌细胞凋亡及半胱氨酸天冬氨酸蛋白酶3的影响

Effect of trimetazidine and ramipril on myocardial cell apoptosis and Caspase-3 expression in heart failure rats

目的探讨曲美他嗪与雷米普利单用及联合应用对慢性心力衰竭大鼠左心室心肌细胞凋亡情况以及半胱氨酸天冬氨酸蛋白酶3(Caspase-3)表达水平的影响。方法雄性Wistar大鼠50只随机分为假手术组、模型组、曲美他嗪组、雷米普利组和联合用药组(曲美他嗪+雷米普利),每组10只。采用肾上腹主动脉缩窄法制作慢性心力衰竭模型,观察各组左心室舒张末压、左心室压力最大上升及下降速率(±dp/dtmax);TUNEL法检测心肌细胞凋亡指数;SP免疫组织化学法检测各组大鼠左心室心肌Caspase-3水平的表达,RT-PCR测定Caspase-3mRNA水平。结果与模型组比较,曲美他嗪组、雷米普利组和联合用药组左心室舒张末压、心肌凋亡指数明显降低,±dp/dtmax明显升高,差异有统计学意义(P<0.01),Caspase-3蛋白及mRNA表达水平明显降低,差异有统计学意义[(0.14±0.01、0.14±0.02和0.08±0.02)vs(0.22±0.02),(0.54±0.02、0.54±0.02和0.32±0.02)vs(0.91±0.02),P<0.01]。结论曲美他嗪与雷米普利单用及联合应用均可有效改善心功能、抑制心肌细胞凋亡,联合用药的疗效优于单独用药。

Objective To study the effect of trimetazidine or ramipril alone and their combination on myocardial cell apoptosis and Caspase-3expression in chronic heart failure rats.Methods Fifty male Wistar rats were randomly divided into sham operation group,model group,trimetazidine group,ramipril group and combined treatment（trimetazidine and ramipril）group（10in each group）.A chronic heart failure model was established by suprarenal aortic constriction.LVEDP and±dp/dtmaxwere recorded,AI of myocardial cells was assayed by TUNEL,expressions of Caspase-3protein and mRNA were detected by SP immunohistochemistry and RT-PCR respectively in different groups.Results The LVEDP,AI and the expression levels of Caspase-3protein and mRNA were significantly lower in trimetazidine group,ramipril group and combined treatment group than in model group（0.14±0.01 vs 0.22±0.02,0.14±0.02 vs 0.54±0.02,0.08±0.02 vs 0.54±0.02,and 0.32±0.02,0.91±0.02,P〈0.01）while the±dp/dtmaxwas significantly higher in trimetazidine group,ramipril group and combined treatment group than in model group.Conclusion Trimetazidine or ramipril alone and their combination can effectively improve cardiac function and inhibit myocardial cell apoptosis in chronic heart failure rats.The therapeutic effect of combined trimetazidine and ramipril is better than that of trimetazidine or ramipril alone.