中药单体调控TGF-β1/Smad信号通路防治糖尿病肾病研究进展  

Research Progress in the Prevention and Treatment of Diabetes Nephropathy by TGF-β1/Smad Signaling Pathway Regulated by Chinese Medicinal Monomers

作　　者：徐思宇 王婉婷 邵命海[1,2,3,4] XU Siyu;WANG Wanting;SHAO Minghai(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,China,201203;Institute of Traditional Chinese Medicine Nephropathy,Shanghai University of Traditional Chinese Medicine,Shanghai,China,201203;Key Laboratory of Liver and Kidney Disease Syndrome of Shanghai University of Traditional Chinese Medicine,Ministry of Education,Shanghai,China,201203;Shanghai Key Laboratory of Traditional Chinese Medicine,Shanghai,China,201203;Guangming Hospital of Traditional Chinese Medicine of Pudong New Area of Shanghai,Shanghai,China,201300)

机构地区：[1]上海中医药大学附属曙光医院,上海201203 [2]上海中医药大学中医肾病研究所,上海201203 [3]上海中医药大学肝肾疾病病证教育部重点实验室,上海201203 [4]上海市中医临床重点实验室,上海201203 [5]上海市浦东新区光明中医医院,上海201300

出　　处：《河南中医》2024年第8期1252-1259,共8页Henan Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81973807)。

摘　　要：转化生长因子(transforming growth factor,TGF)-β1/Smad信号通路是糖尿病肾病肾脏纤维化的关键信号通路之一。TGF-β1/Smad信号通路能通过促进细胞外基质(extracellular matrix,ECM)积聚,抑制ECM的降解,增加纤连蛋白和胶原蛋白Ⅳ表达,促进炎症因子释放,诱导足细胞凋亡等对肾纤维化过程进行调控,部分中药单体可调控TGF-β1/Smad信号通路,显著干预糖尿病肾病的发生发展过程,且取得良好的临床疗效。目前,已初步明确TGF-β1/Smad在糖尿病肾病发生发展中的作用机制,但仍存在许多问题:(1)TGF-β1/Smad信号通路在干性糖尿病肾病和湿性糖尿病肾病中的参与程度和差异不明确;(2)不同功效的中药对纤维化保护性通路发挥正向调节和负向调节作用方向尚不明确;(3)TGF-β1/Smad信号通路会与其他通路形成信号串扰,需探索各条通路间的相互影响机制,并在微观领域深入观察各信号通路对细胞的调控机制;(4)很多中药既能干预TGF-β1/Smad信号通路,又能干预其他通路如自噬、凋亡,在糖尿病肾病的临床治疗中,其疗效的核心机制到底是哪一通路,可能需要精准靶向药物对信号通路进行阻断和促进后,观察疗效的变化来确定;(5)现有的通过调控TGF-β1/Smad治疗糖尿病肾病的临床研究较少,主要以动物实验和基础实验为主,缺少大样本、多中心、前瞻性、长周期的高质量临床试验;(6)目前关于中药有效成分的研究较多,但在中药单体、单体组合方面的研究存在明显不足。今后,需进一步明确TGF-β1/Smad信号通路在干性糖尿病肾病和湿性糖尿病肾病中的参与程度及差异性,明确不同功效的中药对纤维化保护性通路的调节作用,应用分子对接等技术探索中药的有效成分,尤其是对中药单体及单体组合。Transforming growth factor(TGF)-β1/Smad signaling pathway is one of the key signaling pathways of renal fibrosis in diabetes nephropathy.TGF-β1/Smad signal pathway can regulate the process of renal fibrosis by promoting the accumulation of extracellular matrix(ECM),inhibiting the degradation of ECM,increasing the expression of fibronectin and collagen IV,promoting the release of inflammatory factors, inducing podocyte apoptosis and other aspects.Some Chinese medicinal monomers can regulate TGF-β1/Smad signal pathway, significantly interfere with the occurrence and development of diabetes nephropathy, and achieve good clinical effects.At present, the mechanism of TGF-β1/Smad in the occurrence and development of diabetes nephropathy has been preliminarily clarified, but there are still many problems as follows:(1) The participation and difference of TGF-β1/Smad signal pathway in dry diabetes nephropathy and wet diabetes nephropathy are not clear;(2) The direction of the positive and negative regulatory effects of Chinese medicinals with different efficacy on the protective pathway of fibrosis is not yet clear;(3) The TGF-β1/Smad signaling pathway can form signal crosstalk with other pathways, and it is necessary to explore the mutual influence mechanisms between each pathway and observe the regulatory mechanisms of each signaling pathway on cells in a microscopic manner;(4) Many Chinese medicinals can not only interfere with TGF-β1/Smad signal pathway, but also interfere with other pathways such as autophagy and apoptosis.In the clinical treatment of diabetes nephropathy, the core mechanism of its efficacy is to find out certain pathway, and it may need to accurately use target drugs to block and promote the signal pathway, and then observe the changes in efficacy to determine it;(5) The existing clinical studies on the treatment of diabetes nephropathy by regulating TGF-β1/Smad are few, mainly focusing on animal experiments and basic experiments, and lack of large sample, multi-center, prospective, long-te

关 键 词：糖尿病肾病 TGF-Β1/SMAD信号通路 中药单体 

分 类 号：R259.872[医药卫生—中西医结合]