丹芪合剂对糖尿病大鼠肾组织Smurf 2信号通路的调节作用研究  

Effect and Role of Danqi Mixture on Signal Transduction of Smurf 2 in Renal Tissues of Diabetic Rats

作　　者：刘瑞霞[1] 刁宗礼[1] 阴赪宏[1] 王圆圆[2] 郭兵[2] 

机构地区：[1]首都医科大学附属北京友谊医院感染内科,北京100050 [2]贵阳医学院病理生理教研室,贵阳550004

出　　处：《中国实验方剂学杂志》2013年第19期208-212,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金地区基金(81160094);贵州省中药现代化科技产业研究开发专项([2012]5073)

摘　　要：目的:观察丹芪合剂对糖尿病(DM)大鼠肾组织Smad泛素化调节因子2(Smurf 2)表达的影响,初步探讨丹芪合剂抑制糖尿病肾病(DN)的分子机制。方法:链脲佐菌素诱导1型DM大鼠模型,分为正常组、DM组和丹芪合剂1.8 g·kg-1治疗组;12周处死各组大鼠,HE染色观察胰腺和肾组织病理学改变;免疫组化和Western blot测肾组织Smurf 2、核转录共抑制因子(SnoN)、转化生长因子β1(TGF-β1)、磷酸化Smad 2和Smad 3表达。结果:与正常组相比,DM组肾组织Smurf 2蛋白显著增加,SnoN蛋白表达下调,TGF-β1、磷酸化Smad 2和磷酸化Smad 3蛋白上调;与DM组相比,丹芪合剂治疗组Smurf 2蛋白显著减少,SnoN蛋白上调,TGF-β1和磷酸化Smad 2蛋白下调,磷酸化Smad 3无显著差异。结论:丹芪合剂作用机制可能与减少Smurf 2蛋白表达、进而抑制SnoN蛋白泛素化降解有关。Objective： The effective ability of Danqi mixture to inhibit diabetic nephropathy （DN） has been attested in our previous studies. However, the underlying mechanism remains largely unknown. Smad ubiquitination regulatory factor-2 （Smurf 2） is an E3 ubiqutin ligase that plays a pivotal role in regulating transforming growth factor-β1 （TGF-β1） signaling via selectively targeting Ski related novel protein N （SnoN） for degradation. In this study, we investigated the effect of Danqi mixture on expression of Smurf 2, and discuss Danqi mixture＇s possible mechanism in rats with DN. Method： The rat model of diabetes was induced by tail vein injection of streptozotoein. The rats were divided into three groups： the normal group, the model group and the Danqi mixture group （1.8 g·kg^-1 ·d^-1 ）. They were orally administered once a day for 12 weeks. Result： Smurf 2 was predominantly localized to the renal tubular epithelium and interstitium of the kidney, and Western blot analysis revealed that Smurf 2 was up-regulated specifically in renal tissues from the model rats, the Danqi mixture group was significantly reduce the protein levels of Smurf 2 compared to the model group. Interestingly, Danqi mixture was also able to down-regulate the TGF-β1 and phosphorylated Smad 2 （p-Smad 2） , and up-regulate Smad transcriptional corepressor SnoN, but not phosphorylated Smad 3 （p-Smad 3） in kidney. Conclusion： these results indicate that Danqi mixture can targets Smurf 2, maybe via TGF-β1/Smad 2 signaling, thereby providing the ubiquitination degradation of SnoN, so as to mitigate renal functional disorder in DN and delay its development.

关 键 词：丹芪合剂 糖尿病肾病 Smad泛素化调节因子-2 核转录共抑制因子 

分 类 号：R285.5[医药卫生—中药学]