Wu Wei, Huang Yan-Ru, Wan Yi-Gang, Yang Hai-Ming, Mao Zhi-Min, Yang Jing-Jing, Shi Ge, Sun Wei
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.
Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
Zhongguo Zhong Yao Za Zhi. 2016 Jun;41(12):2291-2297. doi: 10.4268/cjcmm20161220.
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.
本研究旨在初步论证尿毒症清除颗粒(UCG)通过在体内调节转化生长因子(TGF)-β1/SnoN/Smads信号通路改善肾间质纤维化(RIF)的作用及机制。将15只大鼠随机分为3组:正常组、模型组和UCG组。采用腺嘌呤灌胃联合单侧输尿管梗阻(UUO)诱导大鼠肾衰竭。造模后,UCG组大鼠与其他组大鼠分别于3周内通过灌胃给予UCG和蒸馏水进行干预。给药后检测所有大鼠的体重及24小时尿蛋白排泄量(Upro)。给药3周后处死所有大鼠,采集血液和肾脏并称重,观察肾脏外观及肾脏形态学特征。此外,分别评估血清生化指标以及肾脏中TGF-β1、SnoN、磷酸化Smad2/3(p-Smad2/3)和Smad7的蛋白表达。结果表明,UCG干预后,模型大鼠的一般健康状况、肾脏外观、血清肌酐(Scr)、血尿素氮(BUN)、尿酸(UA)、白蛋白(Alb)、Upro及肾脏形态学改变均有不同程度改善。此外,UCG下调了肾脏中TGF-β1和p-Smad2/3的蛋白表达,并上调了SnoN和Smad7的蛋白表达。综上所述,UCG可能通过多靶点调节体内TGF-β1/SnoN/Smads信号通路,减少细胞外基质(ECM)合成,延缓肾衰竭进展。