水飞蓟宾对肾间质纤维化模型大鼠肾小管上皮-间充质转分化的影响  

Silybin on Renal Tubular Epithelial-mesenchymal Transdifferentiation in Renal Interstitial Fibrosis Rats

作　　者：刘畅 朱春玲[1] 严瑞[1] 程全伟[1] LIU Chang;ZHU Chunling;YAN Rui;CHENG Quanwei(Department of Kiney Medicine in the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China;Department of Kidney Medicine of Guiyang First People＇s Hospital, Guiyang 550002, Guizhou, China)

机构地区：[1]贵州医科大学附院肾脏内科,贵州贵阳550004 [2]贵阳市第一人民医院肾脏内科,贵州贵阳550002

出　　处：《贵州医科大学学报》2018年第4期394-399,405,共7页Journal of Guizhou Medical University

基　　金：贵州省科技厅社发攻关项目[黔科合SY字(2014)3021号];贵州省科技厅联合基金项目[黔科合LH字(2014)7124号];贵州省卫计委科技基金项目(gzwjki2014-1-007);贵阳市卫计委科学技术计划项目(2015筑卫科技合同字第018号)

摘　　要：目的:探讨水飞蓟宾对肾间质纤维化模型大鼠肾小管上皮-间充质转分化(EMT)的影响。方法:将36只8周龄雄性SD大鼠均分为假手术组(S组)、模型组(U组)、治疗组[水飞蓟宾200 mg/(kg·d)](D组),U组及D组均采用单侧输尿管梗阻复制大鼠肾间质纤维化模型,D组大鼠于术后第1天使用水飞蓟宾灌胃至处死前[200 mg/(kg·d)],S组和U组注射等量生理盐水灌胃;各组大鼠分别于术后第7天、第14天处死6只大鼠,免疫组化染色和Western Blot观察观察Ski、E-钙粘蛋白(E-cadherin)、转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白、Ⅲ型胶原(col-Ⅲ)蛋白的表达,Pearson法分析Ski与TDI、TFI、TGF-β1、α-SMA、col-Ⅲ蛋白表达的相关性。结果:大鼠肾组织免疫组化染色和Western Blot结果显示,与S组比较,U组Ski、E-cadherin蛋白表达明显减少,TGF-β1、α-SMA、col-Ⅲ表达明显升高,第14天时变化更明显(P<0.05);与U组比较,D组大鼠肾组织中Ski、E-cadherin有所增加,但仅第14天差异有统计学意义(P<0.05),TGF-β1、α-SMA、col-Ⅲ显著降低,第14天组更为明显(P<0.05);Pearson相关分析显示,Ski表达与E-cadherin表达呈正相关,而与TGF-β1、α-SMA、col-Ⅲ呈负相关(P<0.05)。结论:水飞蓟宾可能通过Ski影响EMT的发生。Objective： To investigate the effect of silybin on renal tubular epithelial-mesenchymal transdifferentiation（ EMT）. Methods： 36 8-week-old male Sprague-Dawley rats were divided into sham-operation group（ group S）,model group（ group U） and treatment group [silybin 200 mg/（ Kg·d） ]（ group D）. Rats in group U and group D were treated with unilateral ureteral obstruction to induce renal interstitial fibrosis,and the rats in group D were treated with silibin first days after the operation until the death of the stomach [200 mg/（ kg·d） ]. Group S and group U were given the same amount of normal saline intragastric perfusion. Six rats in each group were killed on the 7 th and 14 th day after operation. Immunohistochemical staining and Western Blot were used to observe the expression of E-cadherin,TGF-β1,α-smooth muscle actin and Ⅲ collagen. Pearson analysis was used to analyze the correlation between Ski and the expression of TDI,TFI,TGF-β1,α-SMA and col-Ⅲ protein. Results： Immunohistochemical staining and Western Blot analysis of rat kidney showed that compared with group S,the expression of Ski and E-cadherin protein in group U was significantly reduced,the expression of TGF-β1,α-SMA and col-Ⅲ increased significantly,and the changes were more obvious on the fourteenth day（ P〈0. 05）. Compared with the group U,the renal tissue of rats in group D increased the level of Skio E-cadherin,but the difference was statistically significant only on the 14 th day（ P〈0. 05）. TGF-β1,α-SMA and col-Ⅲ decreased significantly,especially on the 14 th day（ P〈0. 05）. Pearson correlation analysis showed that the expression of Ski was positively correlated with the expression of E-cadherin and negatively correlated with TGF-β1,α-SMA and col-Ⅲ（ P〈0. 05）. Conclusion： Silybin may influence the occurrence of EMT through Ski.

关 键 词：肾间质纤维化 转化生长因子-β1 Α-平滑肌肌动蛋白 肾小管上皮-间充质转分化 水飞蓟宾 

分 类 号：R363[医药卫生—病理学] R963[医药卫生—基础医学]