血管紧张素ⅡⅠ型受体阻断剂抑制大鼠缺血-再灌注模型心肌细胞凋亡

目的观察血管紧张素ⅡⅠ型受体阻断剂losartan对大鼠心肌缺血-再灌注模型心肌细胞凋亡及凋亡相关蛋白P53和Bcl-2表达的影响。方法Wistar大鼠随机分为三组(1)假手术组(5只)；(2)缺血-再灌注组(6只)结扎左冠状动脉45min，再灌注4h；(3)losartan组(6只)缺血前15min和再灌注1h分别静脉注射losartan10mg/kg。采用TUNEL和DNA电泳方法检测心肌细胞凋亡，免疫组织化学方法检测心肌组织P

Angiotensin II type I receptor antagonist losartan reduces apoptosis of cardiomyocytes

Objective　To test the effect of angiotensin II type I receptor antagonist losartan on myocyte apoptosis and expression of P53 and Bcl-2 in myocardium of ischemia-reperfusion rat model. Methods　Wistar rats were randomly divided into three groups:(1) Control group (n=5); (2) Ischemia-reperfusion group(n=6); the left coronary artery was occluded for 45 min followed by 4 hours reperfusion; (3) Losartan group (n=6):losartan (10mg/kg)were given intravenously 15 min before occlusion and 1 hour after the initiation of reperfusion. DNA ladder and TUNEL were used to detect apoptotic myocytes. P53 and Bcl-2 expression in myocardium were analyzed by immunohistochemical technique. Results　The number of apoptotic myocytes of losartan group were 63.6% less than that of ischemia-reperfusion group ［(10.3±2.1)% vs. (28.4±1.4)%, P<0.01］. Ischemia-reperfusion induced P53 expression in myocardium, which could be inhibited by losartan. The expression of Bcl-2 in myocardium were significantly increased in losartan group. Conclusion　Angiotensin II type I receptor antagonist losartan could diminish cardiomiocyte apoptosis induced by ischemia-reperfusion, reduce P53 expression and increase Bcl-2 expression in myocardium.