E-钙黏蛋白在单侧输尿管梗阻模型大鼠肾间质纤维化中的作用

Effect of E-cadherin on renal tubulointerstitial fibrosis in rats with unilateral ureteal obstruction

背景:细胞黏附的丧失及E-钙黏蛋白表达下降在肾小管上皮细胞转分化导致肾间质纤维化疾病进展过程中发挥着的重要作用。目的:观察单侧输尿管梗阻模型大鼠肾小管间质纤维化动态及该病理过程中E-钙黏蛋白、整合素连接激酶蛋白的表达,探讨E-钙黏蛋白在肾小管间质纤维化中的作用机制。方法:72只SD大鼠随机摸球法均分为正常组、对照组和模型组。模型组建立单侧输尿管梗阻模型;对照组仅进行假手术;正常组不做任何处理。分别于造模后第1,3,7,14天分批处死大鼠,检测梗阻侧肾小管间质纤维化损伤程度并检测肾脏组织中E-钙黏蛋白、整合素连接激酶蛋白的表达。结果与结论:与正常组及对照组比较,模型组梗阻时间越长,肾小管间质损害程度越重,纤维化越明显。造模后3d大鼠肾脏组织E-钙黏蛋白mRNA及其蛋白表达水平即出现下调,第14天最低,整合素连接激酶蛋白表达则显著增加,与同期正常组、对照组相比,差异有显著性意义(P<0.05)。说明E-钙黏蛋白的表达减少促进了肾间质纤维化的发生、发展,而整合素连接激酶蛋白的表达增加在肾间质纤维化的进程中可能也发挥了重要作用。

BACKGROUND：The losing of cell adhesion and the decreasing of the E-cadherin expression played the important role in the process for the renal interstitial fibrosis caused by renal tubular epithelial-to-mesenchymal transition.OBJECTIVE：To observe the progress of renal tubule interstitial fibrosis in unilateral ureteral obstruction（UUO） rat models and the expression of E-cadherin and intergrin-linked kinase（ILK） during the pathological course,and to explore the pathogenic role of E-cadherin in renal tubule interstitial fibrosis.METHODS：Seventy-two male Sprague-Dawley rats were randomly divided into normal control group（n=24）,sham-operation group（n=24） and UUO model group（model group,n=24） by touching ball method.Rats in the model group were prepared for UUO model,the rats in the sham-operation group were only preformed with sham-operation,and the normal control group was prepared for nothing.Rats in every group were sacrificed at 1,3,7 and 14 days after operation.The degree of renal tubule interstitial fibrosis on the obstructed side for model group and the expression of E-cadherin and ILK in renal tissues were evaluated.RESULTS AND CONCLUSION：Histological observations of renal tissues revealed that the degree of renal tubule interstitial fibrosis of rats in model group was significantly increased as compared with the normal group and sham-operation group after UUO,and it was increased gradually accompanying with the increasing of obstruction degree.The expression of E-cadherin mRNA and protein of renal tissue in model group began to decrease on the third day after UUO,and reached the minimum at the 14th day,and the protein expression of ILK of renal tissue in model group began to increase on the third day after UUO when compared with the normal group and sham-operation group.Significant difference was assumed among three groups（P 0.05）.It indicated that the lower protein expression of E-cadherin probably promoted the occurrence and development of renal fibrosis,and the higher protein expression of ILK may play an important role in the process of the renal interstitial fibrosis.