黏着斑激酶在2型糖尿病大鼠肾组织中的表达变化及意义  

Role of focal adhesion kinase expression in renal tissues of type 2 diabetic rats

作　　者：李霜[1] 王圆圆[1] 刘丽荣[1] 石磊[1] 石明隽[1] 肖瑛[1] 张国忠[1] 郭兵[1] 

机构地区：[1]贵阳医学院病理生理学教研室,贵州贵阳550004

出　　处：《中国病理生理杂志》2013年第8期1400-1405,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81160094);贵州省社会发展科技攻关计划资助项目(黔科合SY字【2012】3088号)

摘　　要：目的:观察黏着斑激酶(FAK)在2型糖尿病(T2DM)大鼠肾组织中的动态变化,探讨其在糖尿病肾病(DN)发病机制中的作用。方法:复制T2DM模型,随机分为糖尿病8、12和16周(DM8、DM12和DM16)组,另设正常对照(NC)组和高脂高糖对照(HC)组。免疫组织化学检测肾组织中FAK、转化生长因子β1(TGF-β1)、细胞外信号调节激酶1/2(ERK1/2)、p-ERK1/2和纤维连接蛋白(FN)的表达;Western blotting检测FAK和p-FAK(Tyr397)蛋白水平;RT-PCR法检测肾皮质FAK mRNA的水平。结果:DM各组TGF-β1、p-ERK1/2和FN蛋白表达显著高于NC组及HC组(P<0.05);DM12和DM16组肾皮质FAK和p-FAK(Tyr397)表达均较NC组、HC组及DM8组显著增多(P<0.05),且p-FAK(Tyr397)与总FAK蛋白表达趋势一致;FAK与TGF-β1、p-ERK1/2、FN呈显著正相关(P<0.01)。DM12和DM16组FAK mRNA比NC组、HC组及DM8周组表达明显增加(P<0.05)。结论:在2型糖尿病中,FAK可能作为TGF-β1的下游分子被活化,并通过活化ERK1/2使FN表达增多,从而参与了糖尿病肾病的发生发展。AIM： To explore the dynamic change of focal adhesion kinase （FAK） in renal tissues of rats with type 2 diabetes mellitus （T2DM）, and to investigate its role in the pathogenesis of diabetic nephropathy （DN）. METH- ODS： The rat model of T2DM was established and the diabetic rats were randomly divided into 8-week DM （DMS）, 12- week DM （DM12） and 16-week DM （DM16） groups. Meanwhile, normal control （NC） and high-fat high-sucrose control （HC） groups were also established. The protein expression of FAK, transforming growth factor I^l （TGF-131）, extraceUular signal-regulated kinase 1/2 （ERK1/2）, p-ERK1/2 and fibronectin （FN） was detected by immunohistochemical staining. The protein levels of FAK and p-FAK （Tyr397） were detected by Western blotting. The mRNA level of FAK in the renal cortex was examined by RT-PCR. RESULTS： The expression of FAK protein in renal tubular epithelial ceils in DM12 and DM16 groups was significantly higher than that in NC, HC and DM8 groups （P〈0.05）. Moreover, TGF-I^1 , p-ERK1/2 and FN protein expression in DM groups was significantly increased compared with NC and HC groups （P 〈 0.05 ）. The levels of FAK and p-FAK （Tyr397） in the renal cortex in DM12 and DM16 groups were significantly up-regulated com- pared with NC, HC and DM8 groups （P 〈 0.05 ）, and the expression trend of p-FAK in different groups was in accordance with that of total FAK. The FAK protein expression was positively correlated with the expression of TGF-131 , p-ERK1/2 and FN proteins （P 〈 0.01 ）. Compared with NC, HC and DM8 groups, the expression of FAK mRNA increased remarkably in D M 12 and DM16 groups （P 〈 0.05）. CONCLUSION： There is a possibility that FAK is activated as a downstream effector of TGF-[3~ in T2DM, which enhances the expression of FN protein through activating ERK1/2, and therefore plays an important role in the pathogenesis of type 2 diabetic nephropathy. [

关 键 词：糖尿病肾病 黏着斑激酶 转化生长因子Β 细胞外信号调节激酶1 2 

分 类 号：R363[医药卫生—病理学]