摘要
目的探讨血管紧张素Ⅱ(AngⅡ)受体(AT1,AT2)拮抗剂对梗死心肌基质金属蛋白酶(MMPs)及细胞外基质肌腱蛋白(tenascin-c,TN-C)的调节作用。方法结扎大鼠左冠状动脉建立心肌梗死模型,术前7d起分别用安慰剂、AT1受体拮抗剂缬沙坦10mg/(kg.d)、AT2受体拮抗剂PD12331930mg/(kg.d)。术后7d放免法检测左心室游离壁(LVFW)、室间隔(IS)心肌组织基质金属蛋白酶MMP-2,3,9、基质金属蛋白酶组织抑制物-1(TIMP-1)的表达,免疫荧光检测LVFW、IS、RV心肌TN-C的分布。结果与假手术组相比,术后7d手术组、缬沙坦组及PD123319组IS和LVFW的MMP-2,3,9水平显著增加,TIMP-1水平显著减少(P<0.01);TN-C在RV心肌组织及假手术组中不表达,在手术组和PD123319组IS和LVFW中表达增强,缬沙坦组表达较弱。结论AngⅡ参与梗死心肌组织的重构,通过AT1作用于MMPs,调节细胞外基质TN-C等,AT1受体拮抗剂的心脏保护作用与其抑制MMPs及TN-C有关。
AIM To investigate the effect of angiotension Ⅱ （ Ang Ⅱ ） receptors （ AT1. AT2 ） antagonists on matrix metalloproteinases （MMPs） and tenascin-c （TN-C） in infarcted heart of rats. METHODS Rat myocardium infarction （MI） model was established by permanent ligation of the left coronary artery. The infarcted rats were treated respectively with placebo, valsartan （AT1 receptor antagonist, 10 mg/ kg·d） or PD123319 （AT2 receptor antagonist, 30 mg/kg·d）, beginning 7days before induction of myocardial infarction. On the 7th day after MI, the levels of MMP-2,3,9, tissue inhibitors of matrix metal-loproteinase-1 （TIMP-1） were determined by radio immunoassay （RIA） in left ventricular free wall （LVFW） and interventricular septum （IS）. TN-C distribution was also assayed by immunoflorescence. RESULTS In operation, Valsartan and PD123319 group, the levels of MMP-2,3,9 increased in IS and LVFW, whereas the levels of TIMP-1 decreased, with a significant difference from those in sham group （P 〈0.01 ）. There was no expression of TN-C in right cardiac ventricle （RV） and sham groups. TN-C increased in operation and PD123319 groups while decreased in Valsartan group. CONCLUSION Ang Ⅱ is involved in myocardial remodeling in infarcted heart by adjusting MMPs and TN-C via AT1 receptor. The protective effect of AT1 receptor antagonists on the heart may be related to the inhibition of MMPs and TN-C.
出处
《心脏杂志》
CAS
2007年第6期631-634,共4页
Chinese Heart Journal
