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
- Resource Type
- Academic Journal
- Authors
- 齐丽彤; 张钧华; 李大元; 周爱儒
- Source
- 中华心血管病杂志 / CHINESE JOURNAL OF CARDIOLOGY. 29(2):118-121
- Subject
- 氯沙坦
再灌注损伤
脱噬作用
- Language
- Chinese
- ISSN
- 0253-3758
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45 min,再灌注4 h;(3)losartan组(6只):缺血前15 min和再灌注1 h分别静脉注射losartan 10 mg/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(28.4±1.4)%,losartan组凋亡心肌细胞数量显著减少(10.3±2.1)%,P<0.01。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 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.