氯沙坦影响大鼠心肌梗死后心室重塑的机制研究  

Effect of Losartan on Myocardial Remodeling in Myocardial Infarction Rats' Model

作　　者：崔贞玉[1] 韩素霞[1] 冯磊[1] 董晓光[1] 郭李平[1] 常建梅[1] 

机构地区：[1]新疆医科大学第五附属医院心血管内科,新疆维吾尔自治区乌鲁木齐市830054

出　　处：《中国循环杂志》2014年第8期629-633,共5页Chinese Circulation Journal

基　　金：国家自然科学基金(项目批准号:81060023,申请代码:H0207)

摘　　要：目的:探讨血管紧张素转换酶(ACE)2对大鼠心肌梗死(MI)后心肌组织中血管紧张素Ⅱ(AngⅡ)的表达与心肌重塑的影响,进一步阐明氯沙坦对大鼠MI后心肌重塑的作用机制。方法:将32只健康雄性SD大鼠随机分为假手术组、MI组、MI+氯沙坦小剂量组[MI+10 mg/(kg·d)]和MI+氯沙坦大剂量组[MI+20 mg/(kg·d)],各组均8只,随后将MI组和氯沙坦组大鼠建立心尖部MI模型。术中检测梗死前后心电图变化情况。术后24 h开始灌胃给药,给药期1个月,给药结束后测大鼠的血流动力学指标,并取大鼠心尖部心室肌组织,测其重量,随后组织固定切片,苏木素伊红(HE)染色观察心肌组织病理改变情况,逆转录-聚合酶链反应(RT-PCR)法和蛋白印迹(Western Blot)法检测心肌组织ACE2和AngⅡ的mRNA和蛋白表达量。结果:MI组左心室重量及左心室重量指数(LVMI)均明显高于假手术组(P<0.05),左心室射血分数(LVEF)明显低于假手术组(P<0.05),差异均有统计学意义;氯沙坦各组的上述指标均有所改善,呈剂量依赖性。病理结果显示,MI组大鼠梗死区域可见心肌细胞肿胀、破裂,间质增生,炎症细胞浸润明显;MI+氯沙坦大剂量组心肌细胞坏死少见,肿胀减轻;MI+氯沙坦小剂量组居中;假手术组心肌纤维排列规则,无病理改变。MI组心肌内AngⅡ的mRNA和蛋白表达量显著高于假手术组(P<0.05),给予氯沙坦后,表达量呈剂量依赖性下降。MI组心肌内ACE2的mRNA和蛋白的表达量均略高于假手术组(P<0.05),氯沙坦各组继续升高,呈剂量依赖性。结论:氯沙坦可增加大鼠ACE2表达量,进而通过抑制心肌组织内AngⅡ表达来改善MI后的心室重塑。Objective： To investigate the effect of losartan on angiotensin II （Ang II） expression and myocardial remodeling in myocardial infarction （MI） rats’ model. Methods： A total of 32 SD male rats were divided into 4 groups, Sham operation group, MI group, MI with losartan 10mg/（kg·d） group and MI with losartan 20mg/（kg·d）. n=8 in each group. MI model was established and the electrocardiogram changes before and after MI were recorded, hemodynamic indexes were detected at 4 weeks after MI, pathological changes of myocardial tissue were examined by HE staining. The myocardial mRNA and protein expressions of ACE2 and Ang II were detected by RT-PCR and Western Blot analysis. Results： Compared with Sham operation group, MI group showed increased LVMI and decreased LVEF P〈0.05;the above changes were getting better in both MI with losartan groups in a dose-dependent manner. The pathological examination presented that MI group had myocardial cell swelling, fracture, hyperplasia and inflammatory cell infiltration, those damages were less in MI with losartan groups in a dose-dependent manner, Sham operation group had no pathological changes. Compared with Sham operation group, the mRNA and protein expressions of Ang II were obviously higher in MI group, P〈0.05 and the expressions were decreased in MI with losartan groups in a dose-dependent manner;the mRNA and protein expressions of ACE2 were slightly increased in MI group and the expressions were further increased in MI with losartan groups in a dose-dependent manner. Conclusion： Losartan could increase ACE2 expression and therefore, inhibit Ang II expression and improve the ventricular remodeling in MI rats’ model.

关 键 词：血管紧张素转换酶2心 肌梗死 血管紧张素Ⅱ 心肌重塑 氯沙坦 

分 类 号：R541[医药卫生—心血管疾病]