奥马曲拉对心肌梗死大鼠基质金属蛋白酶表达的影响

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。

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

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 ventricular.