E-钙粘蛋白在单侧输尿管梗阻大鼠肾间质纤维化中的作用要点解析.docVIP

E-钙粘蛋白在单侧输尿管梗阻大鼠肾间质纤维化中的作用 程红新1杨晓萍1 赵瑾2 陶林2 （1新疆石河子大学医学院一附院肾病科 新疆石河子832008；2新疆石河子大学医学院病理科 新疆石河子832002） 摘要：目的：观察单侧输尿管梗阻(UUO)模型大鼠肾小管间质纤维化（renal tubulointerstitial fibrosis,RIF）动态进展，研究该病理过程中E-钙粘蛋白（E-cadherin, E-cd）、整合素连接激酶（intergrin-linked kinase ,ILK）的蛋白表达变化，探讨E-钙粘蛋白在肾小管间质纤维化中的作用机制。方法：72只清洁级雄性SD大鼠随机分为正常对照组(n=24)、假手术组(n=24)和UUO模型组(模型组，n=24)。三组大鼠分别于术后(模型组建模后)第1、3、7、14天分批处死(n=6)，留取手术侧(模型组梗阻侧)肾脏组织。分别采用HE和Masson染色、免疫组织化学染色及RT-PCR方法，评价肾小管间质纤维化损伤程度并检测肾脏组织中E-钙粘蛋白、ILK的蛋白表达。结果：肾脏组织形态学显示，与正常组及假手术组比较，梗阻时间越长，模型组肾小管间质损害程度越重，纤维化越明显。免疫组织化学及RT-PCR显示，随着梗阻时间的延长，E-cadherin的mRNA及其蛋白表达水平即出现下调，于第14天达最低值，ILK的蛋白表达则显著增加，与同期正常对照组、假手术组相比，差异具有统计学意义（P0.05）UUO肾纤维化形成过程中，E-cadherin的表达在肾损伤早期即开始减少，并随纤维化程度加重而逐步降低，表明E-cadherin与肾间质纤维化关系密切，E-cadherin的表达减少促进了肾间质纤维化的发生、发展，而ILK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。 关键词：UUO模型; E-钙粘蛋白；整合素连接激酶；肾间质纤维化 THE ROLE OF E-CADHERIN IN UNILATERRAL URETERAL OBSTRUCTION RATS WITH RENAL TUBULOINTERSTITIAL FIBROSIS CHENG Hong-xin ,YANG Xiao-ping,ZHAO Jin;TAO Lin (Department of Nephrology , the First Affiliated Hospital of Shihezi Medical University, Xinjiang 832000, China) Abstract:Objective To observe the progression of renal tubulointerstitial fibrosis in rat unilateral ureteral obstruction(UUO) models， investigate the changes in expression of E-cadherin(E-cd) and intergrin-linked kinase(ILK) during the pathological course, and to explore the pathogenic role of E-cd in renal tubule-interstitium fibrosis. Methods seventy-two male Sprague-Dawley (SD) rats were randomly divided into into normal chtrol group （n =24） 、sham-operation group(n=24) and UUO model group(model group，n=24)．Rats were sacrificed 1，3，7 and 14 d after operation(after model establishment for model group)(n=6 for each day)，and the renal tissues of the operated side(obstructed side for model group) were obtained．HE staining，Masson staining，immunohistochemical staining and reverse transcription polymerase chain reaction(RT-PCR) were used to evaluate the degree of renal tubulointerstitial fibros