心力衰竭大鼠心肌细胞凋亡与依那普利干预治疗效果

EFFECTS OF ENALAPRIL ON MYOCARDIAL APOPTOSIS IN RATS WITH HEART FAILURE

①目的 用依那普利干预治疗大鼠慢性压力负荷性心力衰竭 ,研究心肌重构与心肌细胞凋亡的关系 ,并探讨心力衰竭的发病机制。②方法 30只大鼠随机分为心力衰竭组 (心衰组 ) 1 2只、依那普利治疗组 (治疗组 ) 1 2只以及对照组 8只。通过结扎鼠的腹主动脉复制慢性压力负荷性心力衰竭模型。手术后 6周 ,治疗组给予依那普利1 0mg/ (kg·d)灌胃 ,心衰组和对照组给等量生理盐水灌胃。 1 2周后在测量大鼠血流动力学指标后 ,将大鼠处死 ,取出心脏 ,分别称左心室及心脏质量。用原位脱氧核糖核酸酶末端标记法 (TUNEL)检测心肌细胞凋亡数。③结果 心衰组与对照组相比 ,左心室收缩功能明显减退 (F =2 .80 ,q =2 .4 9,P <0 .0 5 ) ,心肌细胞凋亡数明显增加 (F =98.98,q =1 2 .4 3,P <0 .0 1 )。治疗组心肌细胞凋亡数较心衰组减少 (F =98.98,q=5 .1 9,P <0 .0 1 ) ,心脏质量指数、左心室质量指数均较心衰组减低 (F =1 9.5 6、4 9.34,q =4 .6 1、7.5 6 ,P <0 .0 1 )。 ④结论 心肌细胞凋亡是心室功能减退的重要因素 ,依那普利通过减轻心肌细胞凋亡逆转心室重构 。

Objective To investigate the relationship between myocardial remodeling and apoptosis, and the mechanism of heart failure(HF) in rats with chronic pressure-overload HF treated with enalapril. Methods Thirty rats were randomly divided into heart fai- lure group (HF, n =12), enalapril-treated group (treated group, n =12), and control group ( n =12). The rat model of chronic pressure-overload HF was induced by transverse abdominal aortic constriction. Six weeks after the constriction, the rats in the treated group were la- vaged with enalapril of 10 mg/(kg·d), and those in the other two groups with equal amount of normal saline. Twelve weeks after the constriction, the rats were killed and the hearts removed after the measurement of haemodynamic parameters. The left ventricles and heart were dissected and weighed, respectively. Apoptosis was assessed with TUNEL. Results Compared with the rats in the control group, the HF rats showed a more significant systolic dysfunction ( F=2.80,q= 2.49 , P <0.05), more myocardial apoptosis ( F=98.98,q=12.43, P <0.01). Enalapril treatment reduced myocardial apoptosis ( F=98.98,q=5.19,P <0.01) and improved LV remodeling ( F=49.34,q= 7.56 ,P <0.01). Conclusion Myocardial apoptosis is one of important factors of systolic dysfunction. Enalapril improves LV remodeling by reducing myocardial apoptosis and prevents the progress of HF.