尿毒清颗粒调控TGFβ1SnNSmas信号通路改善肾衰竭模型鼠肾间质纤维化的作用和机制.docVIP

尿毒清颗粒调控TGF P 1/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 ［ ］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) 3 1/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, UU0)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尿蛋白排池: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TGF3 1, SnoN，磷酸化 Smad2/3 (phosphorylated Smad2/3, pSmad2/3)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TGO 1，pSmad2/3 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 P 1/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。 ［关键词］尿毒清颗粒；肾衰竭；肾间质纤维化； SnoN；转化生长因子0 1/Smads信号通路 Effects and mechanisms of UCG ameliorating renal interstitial fibrosis by regulating TGF3 1/SnoN/Smads signaling pathway in renal failure rats WUWeil，2，HUANG Yanru3, WANYigang2, 4*，YANG Haiming2, MAO Zhiminl, YANG Jingjingl，SHI Gel, SUN Wei4 * (1 Department of Traditional Chinese Medicine， Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing 210008 , China； 2 Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China； 3 Division of Molecular Signaling, Department of Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine and Engineering ， University of Yamanashi， Yamanashi 4093898， Japan； 4 Research Institute of Kidney Disease, Nanjing University of Chinese Medicine , Nanjing 210029 , China) [Abstract] 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 ) P 1/SnoN/Smads si