醛固酮受体拮抗剂对心肌梗死大鼠心肌基质金属蛋白酶及其抑制剂的影响  

Effects of Spironolactone on Matrix Metalloproteinases and Tissue Inhibitors of Rats With Myocardial Infarction

作　　者：李侠[1] 董士民[1] 

机构地区：[1]河北医科大学第三医院,石家庄050051

出　　处：《内科急危重症杂志》2008年第1期23-24,31,共3页Journal of Critical Care In Internal Medicine

摘　　要：目的:探讨醛固酮受体拮抗剂影响心室重构的分子机制。方法:大鼠随机分为3组,假手术组、急性心肌梗死(AMI)对照组和螺内酯组,每组均6只。AMI对照组和螺内酯组通过结扎左冠状动脉前降支诱导大鼠AMI模型,螺内酯组用螺内酯进行治疗。应用RT-PCR方法测定非梗死区心肌组织中MMP-2mRNA、TIMP-2mRNA,用免疫组化法测定MMP-2、TIMP-2的蛋白表达。观察分析第2、7、14、21天上述指标的变化。结果:①与假手术组比较,AMI组MMP-2、MMP-2mRNA和TIMP-2、TIMP-2mRNA表达明显升高(P均<0.01);②与AMI组比较,螺内酯组MMP-2、MMP-2mRNA表达在第7、14天及21天时分别降低17%、27%、29%和30%、33%、43%(P均<0.01);TIMP-2、TIMP-2mRNA表达在第7、14天及21天时分别降低了14%、27%、35%和14%、25%、34%(P均<0.01)。结论:心肌梗死大鼠非梗死区MMP-2、TIMP-2转录及表达活性增高,螺内酯能显著降低非梗死区MMP-2、TIMP-2转录及表达活性。Objective： To investigate the effects of the aldosterone receptor antagonism spironolactone on the ventricular remodeling after myocardial infarction. Methods： Rats were randomly divided into sham operation groups,acute myocardial infarction （AMI） group and Spironolactone group（each = 6）. AMI was induced by ligating the left anterior descending coronary artery in the rats. RT-PCR was used to detect the expressions of MMP-2mRNA and TIMP-2 mRNA in the noninfarcted zone. The MMP-2 and TIMP-2 protein was detected by immunohistochemical method. Changes of the above index were analyzed at 2,7, 14 and 21 st days. Results：（1）Expressions of MMP-2, MMP-2 mRNA and TIMP-2, TIMP-2mRNA in noninfarcted zone were increased significantly in AMI group than those in the sham operation group （P〈0. 01）. （2）MMP-2 and MMP-2 mRNA were significantly decreased by 17%, 27% ,29% and 30% ,33% ,43% respectively in spironolactone group compared with those in AMI group at 7,14 and 21st days（P%0. 01）. TIMP-2 and TIMP-2mRNA were significantly decreased by 14% ,27% ,35% and 14%,25%, 34% respectively at 7,14 and 21st days in spironolactone group（P〈0. 01）. Conclusion： Expressions of MMP-2 and TIMP-2 in noninfarcted zone were increased significantly in rats with AMI. Spirolactone may significantly lower the levels of MMP-2 and TIMP-2 in non-infarcted zone.

关 键 词：心肌梗死 心室重构 螺内酯 基质金属蛋白酶 基质金属蛋白酶组织抑制剂 

分 类 号：R542.22[医药卫生—心血管疾病]