EGCG对梗阻性肾病大鼠肾小管上皮细胞转分化的干预作用及机制  

Interventional Effect of EGCG on Transdifferentiation of Renal Tubular Epithelial Cells in Rats with Obstructive Nephropathy and Its Mechanism

作　　者：赵成广[1] 张慧[1] 吴玉斌[1] 

机构地区：[1]中国医科大学附属盛京医院小儿肾脏风湿免疫科,沈阳110004

出　　处：《中国医科大学学报》2011年第6期516-519,共4页Journal of China Medical University

基　　金：沈阳市科学技术计划项目(F10-205-1-29)

摘　　要：目的探讨表没食子儿茶素没食子酸酯(EGCG)对大鼠肾间质纤维化和肾小管上皮细胞转分化的作用及其机制。方法雄性Wistar大鼠56只随机分为正常对照组(n=8)、单侧输尿管梗阻(UUO)模型组(n=24,以单侧输尿管结扎制作肾间质纤维化模型)和EGCG治疗组(n=24,单侧输尿管结扎术后每日给予腹腔注射EGCG 5 mg/kg)。于3,7,14 d分别处死UUO模型组和EGCG治疗组中各8只大鼠,进行HE染色和Masson染色观察肾组织病理变化,免疫组化法检测肾组织中α平滑肌肌动蛋白(α-SMA)、细胞角蛋白18(CK-18)、转化生长因子β(1TGF-β1),Western blot法测定肾组织胞核内核转录因子κB(NF-κB)蛋白表达。结果 UUO组出现肾小管损伤和肾间质纤维化,肾组织中CK-18表达减少,α-SMA和TGF-β1表达增多,肾组织胞核内NF-κB表达增多,而EGCG治疗组较UUO模型组上述改变减轻。结论 EGCG能维持肾小管上皮细胞表型,减轻UUO大鼠模型中肾小管上皮细胞转分化和肾间质纤维化。在体内,EGCG能通过减少TGF-β1的表达和减少NF-κB的活化而减轻肾小管上皮细胞转分化和肾间质纤维化。Objective To explore the mechanism of epigallocatechin-3-gallate （EGCG） and its effect on renal interstitial fibrosis and tubular epithelial cell transdifferentiafion. Methods 56 male Wistar rats were randomly divided into three groups：normal control group （n =8 ）, model group of unilateral ureteral obstruction （UUO） （n =24 ） in which renal interstitial fibrosis model was established by unilateral ureteral ligation and EGCG treatment group （n =24 ） in which EGCG （5 mg/kg） was injected peritoneally on a daily basis after the unilateral ureteral ligafion. 8 rats of each group（the UUO model and EGCG treatment groups）were sacrificed on the 3rd, 7th and 14th day, respectively. The nephfidial histopathology was observed by HE and Masson staining; a-smooth muscle aorta （α-SMA）, cytokeratin 18 （CK-18）, transforufing growth factor-β1 （TGF-β1） in renal tissue were analyzed with inmmnohistochemistry; nuclear factor-κB （NF-κB） protein in nucleus of renal tissue was detected with Western blot. Results In UUO group, renal tubule injury and interstitial fibrosis emerged. Decreased expression of CK-18 and increased expression of α-SMA and TGF-IST in renal tissue,and increased expression of NF-κB in the nucleus of renal tissue were found. But the changes in the EGCG treatment group were less obvious than the UUO model group. Conclusion EGCG can maintain the phenotype of renal tubular epithelial cell and alleviate the transdifferentiation of renal tubular epithelial cell and renal interstitial fibrosis found in UUO model group. In vivo, EGCG can reduce the renal tubular epithelial cell transdifferentiation and renal interstitial fibrosis by down-regulating TGF-β1 expression and decreasing NF-κB activation.

关 键 词：肾间质纤维化 上皮细胞转分化 表没食子儿茶素没食子酸酯 转化生长因子 核转录因子 

分 类 号：R364.3[医药卫生—病理学]