血管紧张素Ⅱ与基质金属蛋白酶及其抑制剂在糖尿病大鼠心肌中的表达及影响

The expression of AngⅡ and metalloproteinases and its inhibitors in the myocardial of diabetic rats and their effect

目的研究糖尿病(DM)大鼠心肌间质重构与血管紧张素Ⅱ(AngⅡ)、转化生长因子(TGF)-β1、基质金属蛋白酶(MMP)-1及其抑制剂(TIMP-1)的关系。方法20只SD大鼠分为正常对照组(10只),DM组(10只),用STZ法建立DM模型,10w时麻醉处死大鼠,免疫组化法检测Ⅰ和Ⅲ型胶原的表达,TGF-β1、MMP-1和TIMP-1蛋白的表达,RT-PCR法检测TIMP-1和MMP-1mRNA的表达。结果DM组心脏指数和左心室指数显著高于正常组(P<0·05),Ⅰ、Ⅲ型胶原的表达也增加,存在着心肌间质重构,同时AngⅡ,TGF-β1,TIMP-1蛋白及TIMP-1mRNA表达增高,MMP-1蛋白及mRNA表达减少(P<0·05)。结论DM大鼠可能因肾素-血管紧张素系统(RAS)的激活,AngⅡ表达增加,直接或间接的影响TGF-β1及MMPs的表达,导致心肌间质重构。

Objective To investigate the expression of Ang Ⅱ, transforming growth factor （TGF）β1, matrix metalloproteinases （MMP） -1 and tissue inhibitors of metalloproteinases （TIMP） -1 in diabetes mellitus （DM） rats and their relation to myocardial interstitial remodification. Methods 20 male SD rats were randomly divided into normal control group and DM group [induced by streptozotocin （STZ） ] , 10 in each group. Ten weeks later,all rats were killed to measure expression levels of type I , m collagen, TGFβ1 protein, MMP-1 and TIMP-1 protein by immunohistochemistry method and detect the mRNA expressions of MMP-1 and TIMP-1 by RT-PCR. Results The cardiac index and the left ventriclular index were significantly higher in DM group than those in normal group（ P 〈 0.05 ）. The expression of AngⅡ ,type Ⅰ , Ⅲ collagen,TGF-β1 protein,TIMP-1 protein and mRNA were also significantly higher in DM group than those in normal group, while the expression of MMP-1 protein and mRNA were significantly lower in DM group （P 〈 0. 05 ）. Conclusions The activation of renin-angiotensin system （RAS） in diabetic rat will increase the expression of Ang Ⅱ , which may directly or indirectly effect the expression of TGFβ1 and MMPs ,all of this will result in the myocardial interstitial remodification of diabetic rat.