中药干预足细胞上皮间质转分化治疗糖尿病肾病的研究进展

Research progress on podocyte epithelial-mesenchymal transition in diabetic nephropathy and interventioneffect of traditional Chinese medicine

糖尿病肾病是终末期肾病的首要原因,足细胞上皮间质转分化(epithelial to mesenchymal transition,EMT)与糖尿病肾病肾功能减退、蛋白尿的发生及进展有重要关系。中医药治疗糖尿病肾病在临床中疗效确切,但糖尿病肾病发病机制复杂,其分子机制尚未完全阐明。足细胞EMT和多条信号通路有关,如转化生长因子-β、Wnt/β-catenin、整合素连接激酶、Notch、丝裂原活化蛋白激酶、核因子-κB、磷脂酰肌醇-3-激酶/蛋白激酶B信号通路,其中转化生长因子-β作为必需细胞因子可激活其他信号通路。信号通路将受到刺激后产生的细胞外信号分子传递进细胞核内与靶基因结合,促进足细胞EMT。中药单体、单味中药如黄芪甲苷、当归多糖、雷公藤甲素、黄芩苷、丹参和生地黄等在体内外实验中被证明对EMT具有一定的抑制作用。本文从信号通路角度,通过将中药干预足细胞EMT的文献进行整合,筛选出作用于足细胞EMT信号通路的中药并对其功效进行分析,发现益气养阴类、清热祛湿类、活血化瘀类中药在足细胞EMT中的研究较多,在糖尿病肾病治疗中可能发挥足细胞保护的机制,为糖尿病肾病的中药治疗提供思路。

Diabetic nephropathy is the leading cause of end-stage renal disease.Podocyte epithelial to mesenchymal transition(EMT) is closely related to the occurrence and progression of renal dysfunction and proteinuria in diabetic nephropathy.Clinical use of traditional Chinese medicine in the treatment of diabetic nephropathy has a significant effect,but the pathogenesis of diabetic nephropathy is complex,and its molecular mechanism has not been fully elucidated.Podocyte EMT is associated with multiple signaling pathways,such as TGF-β,Wnt/β-catenin,ILK,Notch,MAPK,NF-κB,and PI3 K/Akt signaling pathways.TGF-β can act as an essential cytokine to activate other signaling pathways.The signaling pathway transfers extracellular signal molecules generated after stimulation into the nucleus to bind to target genes and promote podocyte EMT.Chinese medicine monomers,single Chinese medicines such as astragaloside,angelica polysaccharide,triptolide,baicalin,salvia miltiorrhiza and rehmannia glutinosa have been shown to have certain inhibitory effects on EMT in vitro and in vivo.In this paper,from the perspective of signaling pathway,through the integration of the literature on Chinese medicine intervention in podocyte EMT,the Chinese medicine intervening on podocyte EMT signaling pathway was screened and its efficacy was analyzed.It was found that there were many studies on Chinese medicine of tonifying qi and nourishing yin,clearing heat and removing dampness and promoting blood circulation and removing blood stasis in podocyte EMT,which may have effects on the mechanisms of podocyte protection in the treatment of diabetic nephropathy and providing new insights for the treatment of diabetic nephropathy with Chinese medicine.