奥马曲拉对心肌梗死大鼠基质金属蛋白酶表达的影响  

Effects of Omapatrilat on the Expression of Myocardium MMP-2,MMP-9 and TIMP-1 After Myocardial Infarction in Rats

作　　者：王静[1,2] 任江华[1] 曹茂银[1] 王玉霞 邹军[1] 

机构地区：[1]武汉大学中南医院心内科,湖北武汉430071 [2]中国航天科工集团731医院内一科,北京100074

出　　处：《武汉大学学报（医学版）》2009年第1期33-37,共5页Medical Journal of Wuhan University

摘　　要：目的:探讨奥马曲拉(Omapatrilat,OMA)对大鼠心肌梗死后基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织因子抑制剂-1(TIMP-1)的表达以及对心室重构和心功能的影响。方法:结扎大鼠冠状动脉左前降支建立心肌梗死模型,术后24 h取实验成功模型大鼠随机分为心肌梗死组(MI组,n=15只)及心肌梗死+OMA治疗组[MI+OMA组,n=15只,OMA 40 mg/(kg.d)饮水给药],另设冠状动脉只穿线未结扎的大鼠为假手术(Sham)组(SH组,n=10只),SH组和MI组大鼠饲普通饮水。治疗后4周测量左室血流动力学,处死动物后测量心室重量指标,行HE染色观察心肌梗死面积,Van Gieson(VG)染色观察胶原容积分数(CVF),Westenblot法测量MMP-2、MMP-9、TIMP-1蛋白表达情况。结果:与SH组比较,手术组大鼠的MMP-2、MMP-9活性显著升高,TIMP-1活性显著降低,心室重构显著,心室功能显著降低;与MI组比较,MI+OMA组可显著降低MMP-2、MMP-9的表达,显著升高TIMP-1的表达,心室功能的改善。结论:OMA可明显抑制大鼠心肌梗死后心室重构,改善心功能,其作用可能与调节MMP-2、MMP-9、TIMP-1的表达有关。Objective： To investigate the effect of vasopeptidase inhibitor on ventricular remodelling, cardiac function, expression of matrix metalloproteinase-2 （MMP-2）, -9 （MMP-9）, and tissue inhibitors of metalloproteinase 1 （TIMP-1） after myocardial infarction in rats. Methods. Male Sprague-Dawley （SD） rats were randomly divided into sham, MI and MI＋Omapatrilat （OMA） group. Myocardial infarction was produced by ligation of the left anterior descending coronary artery. After 24 hours of operation, rats in the MI ＋ OMA group were treated with 40 mg/（kg · d） OMA in their drinking water, and rats in the sham and MI groups were treated with placebo. The hemodynamic and ventricular index, as well as the expression of MMP-2 and -9 protein, TIMP 1 protein and collagen volume fraction （CVF） in the noninfarcted zone was determined in the 4th week after operation. Results： The expression of MMP-2, MMP 9 and TIMP-1 protein in the non-infarcted zone was significantly increased in MI group than that in sham group respectively. OMA significantly reduced MMP-2 and MMP-9 protein expression, increased TIMP-1 protein expression, improved ventricular function and ventricular remodelling. CVF in the MI＋ OMA group decreased than that in the MI group at 4 weeks after operation. Conclusion： The vasopeptidase inhibitor shows favorable effects on left ventricular remodeling after MI in rats and improves cardiac function. These effects may include the downregulation of MMP-2 and MMP-9 expression,and upregulation of TIMP-1 expression in left ventrieular.

关 键 词：OMAPATRILAT 心肌梗塞 基质金属蛋白酶 

分 类 号：R542.2[医药卫生—心血管疾病]