整合素连接激酶在糖尿病肾小管上皮细胞转分化中的作用

Effect of integrin-linked kinase on renal tubular epithelial cell transdifferentiation in diabetic rats

目的:观察整合素连接激酶(ILK)在糖尿病大鼠肾小管上皮细胞中的表达,探讨其与肾小管上皮细胞转分化(EMT)的关系。方法:雄性Wistar大鼠随机分为正常对照组(n=10)、糖尿病模型组(n=10)与糖尿病氯沙坦干预组(n=10)[氯沙坦20mg/(kg.d)];分别于第8周、第16周每组各处死5只大鼠。留取左肾行HE和Masson染色,阅片并计算肾小管间质损伤指数、肾间质胶原面积;免疫组织化学法检测肾小管上皮细胞α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)与ILK的表达。结果:与正常对照组比较,糖尿病组大鼠肾小管间质损伤指数、肾间质胶原面积明显增加(P<0.01),肾小管上皮细胞α-SMA,Vimentin和ILK阳性表达面积明显增加(P<0.01),ILK与α-SMA呈正相关(rs=0.621,P<0.05);氯沙坦组大鼠肾小管间质损伤指数、肾间质胶原面积较糖尿病组明显减弱,其肾小管上皮细胞的ILK,α-SMA与Vimentin表达均较糖尿病组明显减弱(P<0.01)。结论:糖尿病大鼠肾小管上皮细胞存在ILK高表达与EMT,二者之间可能有着重要联系;氯沙坦可下调肾小管上皮细胞ILK表达,阻抑EMT。

Objective To determine the effect of integrin-linked kinase （ILK） in renal tubular epithelial cells and its relation to tubular epithelial-myofibroblast transdifferentiation. Methods Wistar rats were randomly divided into 3 groups ： Group normal control （ n = 10 ） , Group diabetic without therapy（ n = 10）and Group diabetic with Losartan 20 mg/（ kg · d） （n = 10 ）. Five rats were killed in each group at the 8th and 16th week. The left kidneys were kept for HE and Masson staining to observe the pathological variations in the renal interstitium. ILK, α-SMA and Vimentin in renal tubular epithelial cells were detected by immunohistochemistry analysis. Results Compared with the control group, ILK, α-SMA and Vimentin in renal tubular epithelial cells in Group diabetes gradually increased in immunohistochemistry （ P 〈 0.01 ） ; ILK was consistent with the pathological variation of renal interstitium and was positively correlated to α-SMA （ rs = 0. 621 , P 〈 0.05）. In comparison with the Group diabetes, the expression of ILK, α-SMA and Vimentin in renal tubular epithelial cells was apparently declined （ P 〈 0.01 ） in Group diabetes with Losartan. Conclusion Tubular epithelial myofibroblast transdifferentiation and the over-expression of ILK, between which there may be significant connections, are important events in the progression of diabetic nephropathy. Losartan, a blocker of angiotension Ⅱ type Ⅰ receptor, which ILK in diabetic renal tubular epithelial cells, can restrain the transdifferentiation. may down-regulate the expression of procession of epithelial-myofibroblast