缬沙坦对缺血再灌注心肌细胞凋亡及相关基因蛋白表达的影响

Effects of valsartan on apoptotic protein expression in myocardial ischemia reperfusion injury in rats

目的利用大鼠建立心肌缺血再灌注模型,在检测缺血再灌注细胞凋亡变化的同时,着重观察血管紧张素Ⅱ受体(AngⅡ?R)拮抗剂缬沙坦对缺血再灌注心肌细胞凋亡及相关基因蛋白表达的影响,了解AngⅡ?R拮抗剂在心肌缺血再灌注损伤中的作用及其机制,为AngⅡ?R拮抗剂治疗缺血性心脏病提供理论依据。方法 70只Wister大鼠随机分为3组,1组:假手术组(10只);2组:缺血再灌注组(30只);3组:缬沙坦组(30只)。取各组不同时间心肌组织切片,分别应用常规HE染色光镜观察心肌细胞的病理形态变化,免疫组化检测诱导细胞凋亡基因Bax、Fas及抑制细胞凋亡基因bcl-2的表达。结果与假手术组相比,心肌缺血再灌注组Bax和Fas基因蛋白表达明显增加(P<0.01),bcl-2蛋白表达减低(P<0.01)。且随着心肌缺血再灌注时间的延长Bax和Fas基因蛋白表达更加明显。3组经缬沙坦干预后Bax和Fas基因蛋白表达显著减低,而bcl-2蛋白表达增加。结论心肌缺血再灌注时促进心肌细胞凋亡,相关基因蛋白表达增加。AngⅡ?R拮抗剂能够抑制缺血再灌注时心肌细胞凋亡,其机制与逆转Bax、Fas及bcl-2基因蛋白的表达有关。

Objective The ischemia-reperfusion（I-R）heart model was established by ligating the left anterior descending branch of coronary artery in wister rats.To observe the effects of angiotensin Ⅱ type 1 receptor blocker,valsartan on apoptotic protein expression in myocardial ischemia reperfusion injury,and to investigate the preliminary action mechanism of valsartan.Methods Seventy wister rats were randomly divided into three groups,Group I：Sham operated group（n=10）,Group II：Ischemic reperfusion Group（n=30）.Group III：Valsartan group（n=30）.Observed the pathological morphological change of cardiac myocyte with light microscopy after cardiac tissue were handled by H.E separately.The monitoring of proapoptotic Bax and Fas,and antiapoptotic Bcl-2 genes was determined by immunohistochemistry.Results Compared with the sham operated rats,Bax、Fas and Bcl-2 were elevated in Ischemic reperfusion Group and Valsartan group（P〈0.01）,and related to the time of ischemic reperfusion.The expression of Bax and Fas were significantly reduced in Group III but the Bcl-2 was significantly elevated by the treatment of valsartan.Conclusion Myocardial ischemia reperfusion can promote apoptosis and apoptotic protein expression.Ang II-R antagonists can inhibit the ischemia-reperfusion myocardial cell apoptosis,and the mechanism related to reversal of Bax,Fas and bcl-2 protein expression.