福辛普利对慢性心力衰竭大鼠心肌细胞凋亡及相关基因表达的影响

Effect of Fosinppril on Myocardial Cell Apoptosis and Apoptosis-associated Gene Expression in Chronic Heart Failure Rats

目的:探讨福辛普利对慢性心力衰竭大鼠心肌细胞凋亡及相关基因表达的影响。方法:采用肾上腹主动脉缩窄法建立大鼠慢性心力衰竭模型,随机分为假手术组、慢性心力衰竭组、福辛普利组,每组10只大鼠。术后假手术组和慢性心力衰竭组给予生理盐水灌胃,福辛普利组给予福辛普利10 mg/(kg·d)灌胃。8周后,观察各组大鼠左心室舒张末压(LVEDP)、左心室内压最大上升及下降速率(±dp/dtmax)和左心室质量指数(LVMI);脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测大鼠左心室心肌细胞的凋亡指数(AI);SP免疫组织化学染色法检测左心室心肌组织B细胞白血病/淋巴瘤相关抗原2(Bcl-2)、B细胞白血病/淋巴瘤相关抗原相关X(Bax)蛋白的表达;蛋白免疫印记法(Western blotting)检测半胱氨酸天冬氨酸蛋白酶3(Caspase-3)蛋白的表达。结果:慢性心力衰竭组与假手术组相比,大鼠LVEDP、LVMI、心肌细胞凋亡指数、Bax蛋白、Caspase-3蛋白的表达均明显升高(P<0.01),±dp/dtmax、Bcl-2蛋白的表达、Bcl-2/Bax比值显著下降(P<0.01);与慢性心力衰竭组比较,福辛普利组大鼠LVEDP、LVMI、心肌细胞凋亡指数、Bax蛋白、Caspase-3蛋白的表达均明显降低(P<0.01),±dp/dtmax、Bcl-2蛋白的表达、Bcl-2/Bax比值显著升高(P<0.01),差异均有统计学意义。结论:慢性心力衰竭过程中发生了心肌细胞凋亡,福辛普利可通过上调Bcl-2的表达及下调Bax及Caspase-3的表达抑制心肌细胞凋亡,改善慢性心力衰竭大鼠心室功能及心肌肥厚。

Objective： To investigate the effects of fosinppril on myocardial cell apoptosis and apoptosis-associated gene expression in chronic heart failure（CHF） rats. Methods： CHF model was established by partially banding of abdominal aorta superior to renal artery. The experimental rats were randomly divided into 3 groups： Sham operation group and CHF group, the rats in both groups received stomach normal saline; Fosinopril group, the rats received stomach fosinopril 10 mg/kg·d. n=10 in each group and all animals were treated for 8 weeks. LVEDP, ±dp/dtmax and LVMI were examined, left ventricular myocardial cell apoptotic index（AI） was measured by TUNEL method, Bcl-2 and Bax protein levels were detected by immunohistochemistry and caspase-3 protein expression was assessed by Western blotting.Results： Compared with Sham operation group, CHF group had increased LVEDP, LVMI, AI, elevated protein expressions of Bax and Caspase-3, P〈0.01; while decreased ±dp/dtmax, reduced protein expression of Bcl-2 and the ratio of Bcl-2/Bax, P〈0.01. Compared with CHF group, Fosinopril group presented decreased LVEDP, LVMI, AI, reduced protein expressions of Bax and Caspase-3, P〈0.01; while increased ±dp/dtmax, elevated protein expression of Bcl-2 and the ratio of Bcl-2/Bax, P〈0.01.Conclusion： Fosinopril may inhibit myocardial cell apoptosis which occurred during CHF, by up-regulating Bcl-2 expression and down-regulating expressions of Bax and Caspase-3 in CHF rats, therefore improve the cardiac function.