TGF-β相关信号通路在糖尿病病理机制中的作用及中医药干预研究进展  

TGF-β-related Signaling Pathways in Pathogenesis of Diabetes and Prospect of Chinese Medicine Intervention:A Review

作　　者：王晨 程龙 石璐 何昶昊 安永诚 段钰卉 代泓钰 李慧敏 吕迎兰 付宛鑫 黄艳 张慧琳 赵保胜[1] WANG Chen;CHENG Long;SHI Lu;HE Changhao;AN Yongcheng;DUAN Yuhui;DAI Hongyu;LI Huimin;LYU Yinglan;FU Wanxin;HUANG Yan;ZHANG Huilin;ZHAO Baosheng(School of Chinese Materia Medica,School of Life Sciences,Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学中药学院生命科学学院中医药研究院,北京100029

出　　处：《中国实验方剂学杂志》2022年第21期254-263,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(8197140715,82274166)。

摘　　要：现代社会生活方式的改变,特别是高脂饮食和运动量减少使糖尿病发病率日益升高,已成为全球性的公共卫生问题,寻找有效的糖尿病治疗方法日益迫切。转化生长因子-β(TGF-β)信号通路与糖尿病并发症、肿瘤关系的研究较多,但其在糖尿病发生的作用尚未阐明。TGF-β信号通路可被多种因素激活,直接或间接导致胰岛β细胞凋亡和胰岛素抵抗(IR),有望成为糖尿病治疗的重要新靶点。TGF-β相关信号通路包括腺苷酸活化蛋白激酶(AMPK)、糖基化终产物受体、c-Myc、SnoN、Smurf1、miR-335-5P等信号分子,参与IR、胰岛β细胞凋亡、胰岛素分泌障碍、脂肪细胞纤维化表型及脂肪细胞代谢障碍的发生发展,并抑制白色脂肪棕色化,在人类糖尿病病理过程中发挥重要作用。中医认为糖尿病的病机为气阴两虚,后期除气虚外兼有阳虚血瘀,治以益气养阴,后期兼有温阳活血。研究发现部分中药和复方治疗糖尿病的作用与其对TGF-β信号通路的抑制高度相关。现综述TGF-β信号分子相关多条信号通路,阐明其在糖尿病形成过程中的病理机制,并就治疗糖尿病的中药复方与TGF-β信号通路相关性进行展望性分析。为治疗糖尿病的研究提供一定的理论依据。The incidence of diabetes has been on the rise as the result of lifestyle changes,especially the high-fat diet and reduced exercise.Thus,it has become a global public health problem and it is an urgent task to explore effective therapy.There has been an explosion of research on the relationship of transforming growth factor-β(TGF-β)signaling pathways with diabetes complications and tumors,but the role of the pathways in the occurrence and progression of diabetes remains unclear.TGF-β signaling pathways can be activated by many factors,directly or indirectly leading to the apoptosis of islet β cells and insulin resistance(IR),and thus they are expected to become new targets for the treatment of diabetes.TGF-β-related signaling pathways involve AMPactivated proteinkinase(AMPK),protooncogene(c-Myc),Ski-relatednovel protein N(SnoN),Smad ubiquitination regulatory factor 1(Smurf1),miR-335-5p,and other signaling molecules.They participate in the occurrence and development of IR,apoptosis of islet β cells,insulin secretion disorder,fibrosis of adipocytes,and metabolic disorder of adipocytes,and inhibit the browning of white adipose tissue,playing an important part in the pathological process of human diabetes.According to traditional Chinese medicine(TCM),the pathogenesis of diabetes is the deficiency of Qi and Yin,and the late stage is characterized by the syndrome of Qi deficiency,and Yang deficiency and blood stasis,which should be treated according to the principle of replenishing Qi and nourishing Yin,warming Yang and activating blood.It has been found that the efficacy of some Chinese medicinals and compound prescriptions on diabetes is closely related to the TGF-β signaling pathways.This paper reviews TGF-β-associated signaling pathways,elucidating the roles of them in pathogenesis of diabetes,and analyzes the relationship of TGF-β-associated signaling pathways with the effect of compound Chinese medicine prescriptions against diabetes.This study is expected to lay a theoretical basis for the research on

关 键 词：转化生长因子-(βTGF-β) 糖尿病 胰岛素抵抗 胰岛Β细胞 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学] R2-031R285.5