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

Angiotensin II type I receptor antagonist losartan reduces apoptosis of cardiomyocytes

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losartan 10mg/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P53 和Bcl 2蛋白表达。结果 缺血 再灌注组凋亡心肌细胞数量为 (2 8.4± 1.4) % ,losartan组凋亡心肌细胞数量显著减少 (10 .3± 2 .1) % ,P <0 .0 1。缺血 再灌注组心肌P53 表达增加。losartan抑制P53 的表达 ,增加Bcl 2表达。结论 缺血 再灌注过程中大鼠心肌细胞可以发生凋亡 ,血管紧张素ⅡⅠ型受体阻断剂可减少心肌细胞凋亡的数量 ,抑制心肌P53 的表达、促进Bcl 2的表达。

Objective To test the effect of angiotensin II type I receptor antagonist losartan on myocyte apoptosis and expression of P 53 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. P 53 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 P 53 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 P 53 expression and increase Bcl 2 expression in myocardium.