目的:探讨心力衰竭大鼠心肌细胞凋亡与心功能的关系及福辛普利和氯沙坦的干预作用。方法:雌性SD大鼠行左前降支结扎术致急性心肌梗死,术后4周行多普勒超声心动图检测,成功制作慢性心力衰竭(左心室射血分数≤0.45)大鼠36只,随机分成:福辛普利组(50mg/kg·d,n=12);氯沙坦组(30mg/kg·d,n=12);生理盐水组(1ml/d,n=12)。另设假手术组(n=8)不结扎冠状动脉。治疗8周后,再次行超声心动图检测。原位末端标记法(TUNEL)和脱氧核糖核酸(DNA)梯形谱(DNA ladder)检测心肌细胞凋亡。结果:3组心力衰竭大鼠DNA电泳均显示凋亡特征性DNA ladder。与假手术组比较,生理盐水组各项心功能指标显著下降,凋亡指数显著升高(P〈0.05)。与生理盐水组比较,福辛普利组和氯沙坦组各项心功能指标显著改善,福辛普利组(P〈0.05)和氯沙坦组(P〈0.05)凋亡指数显著降低。左心室射血分数与临近梗塞区心肌凋亡细胞数量之间呈负相关关系(r=-0.754,P〈0.001)。结论:心肌细胞凋亡与心力衰竭时心功能不断恶化相关。福辛普利和氯沙坦能抑制心肌细胞凋亡并改善左心室收缩功能。
Objective : To analyze the correlation between cardiomyocyte apoptosis and left ventricular function in rats with chronic heart failure(HF) , and evaluate the effects of fosinopril and losartan on cardiomyocyte apoptosis and left ventricular function. Methods: Four weeks after coronary ligation, left ventricular function of survival rats was measured with high frequency Doppler echocardiography. Thirty sex rats with LV ejection fraction ≤0.45 were randomized to three groups: HF-F (fosinopril, 50 mg/kg·d,n=12), HF-L (losartan, 30 mg/kg·d,n=12) and HF-C (placebo,n=12). Sham-operated rats (n =8) served as controls. Eight weeks of treatment, LV function was assessed again by echocardiography. The cardiomyocyte apoptosis was examined by in situ TDT-mediated dUTP nick and labeling and electrophoretic detection of DNA laddering. The correlation between cardiomyocyte apoptosis and left ventricular function was analyzed. Results: DNA laddering was shown in the cardiac myocytes of the rats with heart failure by agarose gel electrophoresis of DNA fragments. Compared with shamed-operated rats, ejection fraction of HF-C was decreased significantly, and the cardiomyocyte apoptosis index(APOI) was significantly higher ( P 〈 0. 05 ). After treatment, compared with HF-C, ejection fraction of HF-F or HF-L was increased significantly. Compared with HF-C, APOI was significantly lower in HF-F (P 〈 0. 05 ) and HF-L (P 〈 0. 05 ). APOI can exert a negative influence on the left ventricular ejection fraction (r = -0. 754, P 〈 0. 001 ). Conclusion: The results of this study indicate that there is a negative correlation between cardiomyocyte apoptosis and left ventricular function. Losartion and fosinopril can attenuate progressive deterioration of global left ventricular function and inhibit cardiomyocyte apoptosis in rats with heart failure.