尿毒清颗粒调控TGF-β1/SnoN/Smads信号通路改善肾衰竭模型鼠肾间质纤维化的作用和机制  

Effects and mechanisms of UCG ameliorating renal interstitial fibrosis by regulating TGF-β1/ SnoN/Smads signaling pathway in renal failure rats

作　　者：吴薇[1,2] 黄燕如 万毅刚[2,4] 杨海明[2] 毛志敏[1] 杨晶晶[1] 石格 孙伟[4] 

机构地区：[1]南京中医药大学中西医结合鼓楼临床医学院中医科,江苏南京210008 [2]南京大学医学院附属鼓楼医院中医科,江苏南京210008 [3]Division of Molecular Signaling,Department of Advanced Biomedical Research,Interdisciplinary Graduate School of Medicine and Engineering,University of Yamanashi [4]南京中医药大学肾病研究所,江苏南京210029

出　　处：《中国中药杂志》2016年第12期2291-2297,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81374030;81573903)

摘　　要：为了初步阐明尿毒清颗粒(uremic clearance granule,UCG)在体内调控转化生长因子(transforming growth factor,TGF)-β1/SnoN/Smads信号通路而改善肾间质纤维化(renal interstitial fibrosis,RIF)的作用和机制,将15只大鼠随机分为正常组、模型组、尿毒清组。采用腺嘌呤灌胃联合单侧输尿管结扎术(unilateral ureteral obstruction,UUO)建立肾衰竭模型。造模后,3组大鼠分别给予UCG悬浊液或蒸馏水,共3周,其间,检测大鼠体重、24 h尿蛋白排泄量(urinary protein excretion,Upro);给药3周后,处死全部大鼠,抽取血液,摘除双肾,称重,观察肾脏外观和肾组织形态特征,检测血清生化指标和肾组织TGF-β1,SnoN,磷酸化Smad2/3(phosphorylated Smad2/3,p-Smad2/3)以及Smad7蛋白表达量。结果表明,经UCG干预后,模型鼠一般情况,肾脏外观、血清肌酐(serum creatinine,Scr)、血清尿素氮(blood urea nitrogen,BUN)、尿酸(uric acid,UA)、白蛋白(albumin,Alb)、Upro以及肾组织形态均得到不同程度的改善;UCG还可以下调模型鼠肾组织TGF-β1,p-Smad2/3蛋白表达水平,上调SnoN,Smad7蛋白表达水平。总之,UCG可能在体内多靶点地调控TGF-β1/SnoN/Smad信号通路,从而,减少细胞外基质(extracellular matrix,ECM)合成,延缓肾衰竭进展。This study was aimed to demonstrate preliminarily the effects and mechanisms of uremic clearance granule（ UCG） ameliorating renal interstitial fibrosis（ RIF） by regulating transforming growth factor（ TGF）-β1 / SnoN / Smads signaling pathway in vivo. Fifteen rats were randomly divided into 3 groups： the normal group,the model group and the UCG group. The rats with renal failure were induced by intragastric administration of adenine and unilateral ureteral obstruction（ UUO）. After modeling,the rats in the UCG group and in the other groups were intervened by intragastric administration of UCG and distilled water respectively during 3 weeks. The body weight and 24 h urinary protein excretion（ Upro） in all rats were tested after drug administration. All rats were killed after drug administration for 3 weeks,blood and kidneys were collected and weighted,kidney appearance and renal morphological characteristics were observed. In addition,serum biochemical indices and the protein expressions of TGF-β1,SnoN,phosphorylated Smad2 /3（ p-Smad2 /3）and Smad7 in the kidney were evaluated respectively. The results indicated that,after the intervention of UCG,the general state of health,kidney appearance,serum creatinine（ Scr）,blood urea nitrogen（ BUN）,uric acid（ UA）,albumin（ Alb）,Upro and renal morphological change in model rats were improved in different degrees,respectively. Moreover,UCG down-regulated the protein expressions of TGF-β1 and p-Smad2 /3,and up-regulated the protein expressions of SnoN and Smad7 in the kidney. In conclusion,UCG reduces extracellular matrix（ ECM） synthesis and delays the progression of renal failure via possibly multi-targeting at regulating TGF-β1 / SnoN /Smads signaling pathway in vivo.

关 键 词：尿毒清颗粒 肾衰竭 肾间质纤维化 SNON 转化生长因子-β1/Smads信号通路 

分 类 号：R285.5[医药卫生—中药学]