基于TGF-β/Smads信号通路探讨肾康注射液对输尿管结扎模型小鼠的作用  

Effects of Shenkang Injection on ureteral ligation model mice based on TGF-β/Smads signaling pathway

作　　者：邹俊驹 周晓韬 陈鲜[2] 王丽[2] 马跃荣 ZOU Jun-ju;ZHOU Xiao-tao;CHEN Xian;WANG Li;MA Yue-rong(School of Basic Medicine,Chengdu University of TCM,Chengdu 611137,China;Department of Pathology,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China)

机构地区：[1]成都中医药大学基础医学院,成都611137 [2]成都中医药大学附属医院病理科,成都610075

出　　处：《中华中医药杂志》2021年第5期2629-2634,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81473522,No.81973732);四川省中医药管理局科学技术研究专项课题(No.2020JC0040)。

摘　　要：目的:通过观察肾康注射液对输尿管结扎(UUO)模型小鼠E3泛素连接酶Smurf2介导TGF-β/Smads信号通路的影响,探索其抗肾间质纤维化的作用机制。方法:将50只C57BL/6J小鼠随机分成5组,即假手术组、UUO模型组、肾康注射液高剂量组、肾康注射液中剂量组、肾康注射液低剂量组,每组10只。通过左侧输尿管结扎手术制备UUO动物模型,观察血清中肌酐和尿素氮、肾脏组织形态、Smurf2及TGF-β信号通路相关蛋白的表达情况。结果:肾康注射液可减轻UUO引起肾功能的异常,并可通过减少肾小管的扩张、胶原蛋白沉积和肾小管间质腔扩张来改善肾小管间质损伤和纤维化;此外,肾康注射液通过促进Smad7与E3泛素链接酶Smurf2的表达,使TGF-β1的Ⅰ型受体、P-Smad2/3泛素化降解。结论:肾康注射液可以通过泛素化的方式调节UUO模型小鼠中的TGF-β/Smad信号通路,减轻肾间质纤维化。Objective:To investigate the effects of Shenkang Injection on the E3 ubiquitin ligase Smurf2-mediated TGF-β/Smads signaling pathway in ureteral ligation(UUO)model mice,and to explore the mechanism of its anti-renal interstitial fibrosis.Methods:Fifty C57 BL/6 J mice were randomly divided into 5 groups,namely sham operation group,UUO model group,Shenkang Injection high dose group,Shenkang Injection medium dose group,and Shenkang Injection low dose group,10 in each one.The UUO animal model was prepared by ligation of the left ureter to observe the expression of serum creatinine and urea nitrogen,renal tissue morphology,Smurf2 and TGF-βsignaling pathway related proteins.Results:Shenkang Injection could alleviate renal dysfunction caused by UUO,and ameliorate renal tubular damage and fibrosis by reducing tubules dilation,collagen deposition and tubulointerstitium dilatation.In addition,by promoting the expression of Smad7 and E3 ubiquitin linker Smurf2,Shenkang Injection degraded the typeⅠreceptor(TβR-Ⅰ)and P-Smad2/3 ubiquitin of TGF-β1.Conclusion:Shenkang Injection can regulate TGF-β/Smad signaling pathway in UUO model mice by ubiquitylation,and alleviate renal interstitial fibrosis.

关 键 词：肾纤维化 上皮-间充质转化 肾康注射液 TGF-β/Smads信号通路 E3泛素连接酶Smurf2 

分 类 号：R285.5[医药卫生—中药学]