肾康注射液调节TGF-βⅠ型受体/Smad通路抑制肾纤维化的作用机制  

Regulation of the TGF-β type I Receptor/Smad Pathway Inhibits Renal Fibrosis by Shenkang Injection

作　　者：崔天梦 黄更珍 张莹莹 马跃荣 Cui Tianmeng;Huang Gengzhen;Zhang Yingying;Ma Yuerong(School of Basic Medicine,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610075

出　　处：《世界科学技术-中医药现代化》2023年第10期3355-3363,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然基金委员会面上项目(81973732):固本化瘀通络法抗肾纤维化的Smad3/Smad7平衡通路分子机制研究,负责人:马跃荣

摘　　要：目的肾康注射液(Shenkang injection,SKI)作为一种中药静脉注射剂,已在临床用于治疗慢性肾病。本研究探讨SKI调节TGF-βⅠ型受体/Smad通路抑制肾纤维化的作用机制。方法在37℃环境中,使用10 ng·mL^(-1)TGF-β1处理人小管上皮细胞(Human kidney proximal tubular cell,HK-2)48 h,建立体外肾纤维化模型。用SKI处理细胞48 h后,通过显微镜观察细胞的形态;采用Western blot、RT-PCR和免疫荧光技术检测α-平滑肌肌动蛋白(α-Smooth muscle actin,α-SMA)、Ⅲ型胶原(Collagen typeⅢ,COI-Ⅲ)、TGF-β1、Smad3、Smad7和TβR-Ⅰ蛋白和基因的表达变化。结果SKI能抑制肾纤维化相关蛋白和基因的表达,如α-SMA和COI-Ⅲ。SKI调控与TGF-β/Smad信号通路相关蛋白的表达,通过下调TGF-β1、Smad3和TβR-Ⅰ蛋白,上调Smad7蛋白表达,延缓肾脏纤维化。结论SKI抑制肾纤维化,可能通过下调TβR-Ⅰ、调控TGF-β/Smad通路相关分子的表达。Objective Chinese herbal injections called Shenkang injections(SKI)have become widely used for treating chronic kidney disease in the clinic.An investigation into the underlying mechanisms of SKI inhibition of renal tubular epithelial cell trans differentiation treated with TGF-β1 was carried out in this study.Methods To create an in vitro model of RF,HK-2 cells were treated with TGF-1(10 ng·mL^(-1))at 37℃for 48 h.After the cells were treated with SKI for 48 h,the morphology of the cells was observed by electron microscope.And Western blot,RT-PCR and immunofluorescence techniques were used to detectα-Smooth muscle actin(α-SMA),type III collagen(COI-Ⅲ),TGF-β1,Smad3,Smad7 and TβR-I expression changes of proteins and genes.Results SKI can significantly reduce expressed proteins and genes related to renal fibrosis,such asα-Smooth muscle actin(α-SMA)and typeⅢcollagen(COI-Ⅲ).SKI control the production of proteins associated with the TGF-β/Smad signaling pathway.By downregulating TGF-β1,Smad3,and TβR-I protein expression,as well as upregulating Smad7 protein expression,it is able to prevent cell trans differentiation.Conclusions SKI can inhibit renal tubular epithelial cell mesenchymal trans differentiation.In addition,this drug may prevent chronic kidney disease by downregulating the expression of TβR-I and regulating the TGF-β/Smad pathway-related molecules.

关 键 词：肾康注射液 肾纤维化 TβR-Ⅰ型受体 HK-2细胞 TGF-Β/SMAD信号通路 

分 类 号：R285.5[医药卫生—中药学]