氯沙坦对大鼠心肌缺血后心脏ACE2蛋白表达的影响

Effect of losartan on cardiac ACE2 protein expression in myocardial ischemia rat

目的探讨氯沙坦对心肌缺血大鼠心肌组织中ACE2表达水平的影响。方法 SPF级健康雄性SD大鼠60只（体重220-240 g）,通过部分结扎冠状动脉前降支建立大鼠心肌缺血模型,将术后24 h存活的42只大鼠随机分为14 d模型组、28 d模型组、14 d氯沙坦大剂量组、14 d氯沙坦小剂量组、28 d氯沙坦大剂量组、28 d氯沙坦小剂量组、假手术组,每组6只。术后24 h开始灌胃给药,小剂量氯沙坦组10 mg/（kg·d）灌胃给药,大剂量氯沙坦组30 mg/（kg·d）灌胃给药,假手术组及模型组给予等量生理盐水灌胃;分别于用药14 d、28 d后,行HE染色,明确心肌组织缺血病变情况,Western blot法检测左心室缺血区心肌组织ACE2蛋白表达的水平。结果模型组大鼠缺血心肌组织中ACE2蛋白表达量较假手术组升高（P〈0.01）,呈时间依赖性。氯沙坦剂量依赖性增加ACE2蛋白的表达量（P〈0.05）。结论氯沙坦可增加心肌缺血后大鼠心肌组织中ACE2的表达量,进一步改善心肌缺血状态。

Objective To investigate the effect of losartan on cardic ACE2 protein expression in myocardial ischemia rat. Methods Myocardial ischemia rat model was established by ligation of the anterior descending coronary artery. Twenty-four hours after the procedure,the 42 surviving rats were randomly divided into model with 14 or 28 d group（n = 6）,losartan large dose treatment with 14 or 28 d group（n = 6）,losartan low dose treatment with 14 or 28 d group（n = 6） and Sham group（n = 6）. The rats in losartan large and low dose groups were treated respectively with10 mg /（kg·d） and 30 mg /（kg·d） of losartan,rats in sham group were treated with equal quantity physiological saline. The pathological changes of myocardial was observed by HE staining,the relative expression of myocardium ACE2 protein was assessed by Western-blot. Results The protein expression of ACE2 in model group were increased compared with sham group in time dependence（ P〈0. 05）. The ACE2 protein level of myocardiac with losartan treated group was significantly increased in dose-time dependence compared with the non-treated ones（P〈0. 05）. Conclusion Large-dose losartan can improve the myocardial ischemia status by increasing the ACE2 expression in myocardium of rats.