氯沙坦干预对心衰大鼠心肌细胞凋亡和Ca~(2+)变化的影响

目的:研究氯沙坦干预心肌细胞凋亡和细胞内钙调节的作用,探讨血管紧张素型受体阻断剂治疗心力衰竭的机制。方法:采用阿霉素腹腔注射复制心衰模型,氯沙坦干预组给予氯沙坦干预。透射电镜观察心肌超微结构改变,测定血清中CPK、CK-MB的含量。检测大鼠心肌细胞凋亡及心肌组织匀浆中Ca2+的变化。结果:心衰组与氯沙坦干预组相比,心肌组织中CPK、CK-MB活力降低。心肌细胞严重损伤,并可见凋亡小体,心肌细胞凋亡指数明显增加(P<0.01)。与对照组相比,心衰组心肌组织中的Ca2+含量升高(P<0.01);氯沙坦干预组与心衰组相比Ca2+显著降低(P<0.01)。结论:心力衰竭时发生了心肌细胞凋亡,氯沙坦可有效抑制心肌细胞凋亡,减轻心肌超微结构受损,减少心肌酶外漏。心衰时心肌组织匀浆中Ca2+增加,可能是肌浆网钙泵活性受损。氯沙坦有抑制心肌细胞凋亡及Ca2+超载,改善心力衰竭的作用。

Effects on rat heart failure cells and changes of Ca~(2+) by intervention of losartan

Objective：To study the effects on heart failure cells and intracellular Ca2＋ regulation by intervention of losartan,and discuss the mechanism of angiotensin-receptor（type-Ⅰreceptor）blockers in the treatment of heart failure.Methods：To copy the heart failure model by injecting Doxorubicin into abdominal cavity,losartan was administrated in losatan intervention group.To observe the changes of microstructure of myocardial cells by means of transmission electron microscope and assay the amounts of CPK、CK-MB in serum.To detect apoptosis in rat myocardial cells and change of Ca2＋ in homogenate of myocardial tissues.Results：Comparison of heart failure group with losatan intervention group,activities of CPK,CK-MB in myocardial tissues decrease.Myocardial cells are heavily injured and there is apoptotic body,Apoptosis index of myocardial cells elevates apparently（P0.01）.In comparison with control group,the amount of Ca2＋ elevates in myocardial tissues in heart failure group（P 0.01）;Comparison of losatan intervention group with heart failure group,the amount of Ca2＋ remarkably decreases（P0.01）.Conclusion：Myocardial cells undergo apoptosis when HF occurs,while losartan can effectually inhibit apoptosis of myocardial cells,lighten the damage of microstructure of myocardial cells and decrease the outleakage of myocardial enzyme.There are increased amount of Ca2＋ in homogenate of myocardial tissues,to which may be contributed by the impared activity of Ca2＋--pump in sarcoplasmic reticulum.Losartan can effectually inhibit apoptosis of myocardial cells and calcium overload,and improve HF.