奥帕曲拉对大鼠心肌梗死后肿瘤坏死因子-α、基质金属蛋白酶-2的表达及心室重构的影响  

Effect of omapatrilat on myocardium TNF-α、MMP-2 expression and ventricular remodeling (after) myocardial infarction in rats

作　　者：官洪山[1] 王虹[1] 上官海娟[2] 哈黛文[1] 赵艳锋[3] 

机构地区：[1]武汉大学中南医院老年病研究室,湖北武汉430071 [2]新乡医学院第一附属医院,河南卫辉453100 [3]武汉大学医学院生理系,湖北武汉430071

出　　处：《中国医院药学杂志》2006年第5期545-548,共4页Chinese Journal of Hospital Pharmacy

摘　　要：目的:探讨血管肽酶抑制剂对心肌梗死后心力衰竭大鼠心肌肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)的表达以及心室重构和心室功能的影响。方法:结扎大鼠冠状动脉前降支建立心肌梗死模型,术后24h存活大鼠分为心肌梗死组(MI组)和心肌梗死奥帕曲拉(omapatrilat,OMA)干预组(MI+OMA组,OMA40mg.kg-1.d-1,饮水给药),另设sham组,sham组和MI组大鼠饲普通饮水。术后6周检测各组心室重构指标、左室血流动力学以及TNF-α、MMP-2蛋白的表达。结果:与sham组相比,心肌梗死6周末MI组大鼠TNF-α、MMP-2的表达明显增加,心室重构显著,心室功能明显降低;OMA显著降低心肌梗死后TNF-α、MMP-2的表达伴心室重构和心功能的改善。结论:血管肽酶抑制剂能够明显减轻大鼠心肌梗死后心室重构,改善心室功能,其作用可能与调节心脏TNF-α和MMP-2的表达有关。IBHECTUVE To investigate the effect of vasopeptidase inhibitor on ventricular remodeling, cardiac function,tumor necrosis factor-α protein and matrix metalloprotelnase-2 after myocardial infarction in rats. METHODS Male SpragueDawley （SD） rats were randomly divided into three groups; sham, MI and MI ＋ omapatrilat （OMA）. 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^-1·d^-1 OMA in their drinking water, and rats in the sham and MI groups were treated with placebo. Determine the hemodynamic and ventricular index as well as the expression of TNF-α protein and MMP-2 protein at 6 weeks after operation. RESULTS The expression of TNF-α protein and MMP-2 protein in the non-infarcted zone were significantly increased in MI group than in sham group. OMA significantly reduced TNF-α protein and MMP2 protein expression, improved ventricular function and ventricular remodeling. CONCLUSION The vasopeptidase inhibitor shows favorable effects on left ventricular remodeling after MI in rats and improves cardiac function. These effects could be relevant to the attenuation of increased MMP-2 and TNF-α in left ventricular.

关 键 词：奥帕曲拉 心肌梗死 心室重构 肿瘤坏死因子-Α 基质金属蛋白酶-2 

分 类 号：R965.1[医药卫生—药理学]