AGEs-RAGE信号通路在糖尿病肾病中的作用机制及中医药研究进展

The Mechanism of AGEs-RAGE Signaling Pathway in Diabetic Nephropathy and the Progress of Chinese Medicine Treatment

糖尿病肾病是临床常见的糖尿病并发症,是导致终末期肾脏病的主要原因之一,也是糖尿病患者致死的重要因素之一。晚期糖基化终末产物(advanced glycosylation end products,AGEs)-糖基化终末产物受体(receptor of AGEs,RAGE)信号通路是糖尿病肾病发生发展的重要一环,在糖尿病肾病中的作用机制主要有激活核转录因子-κB(nuclear factor-κB,NF-κB),刺激产生血管内皮生长因子(vascular endothelial growthfactor,VEGF),刺激转化生长因子-β1(transforming growth factor-β1,TGF-β1)的产生,诱导单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)表达的增强,激活P21肾素-血管紧张素导致细胞功能紊乱,激活烟酰胺腺嘌呤二核苷酸磷酸(nicotinamide adenine dinucleotide phosphate,NADPH)氧化酶引起氧化应激等。中医药治疗糖尿病肾病具有整体调节和多通道、多靶点的优势,可通过阻断AGEs-RAGE信号通路改善糖尿病肾病进展。目前研究存在的问题主要有:AGEs-RAGE下游机制复杂,未完全阐明,其与一些关键因子如NF-κB、VGEF、TGF-β1、MCP-1基因的关系还有待进一步研究证实;单味中药和中药复方的活性成分治疗糖尿病肾病的临床研究和动物实验较多,但针对AGEs-RAGE信号通路的研究较少;目前实验大多于体外进行,其机制和作用靶点尚未明确。今后的研究中,需进一步完善实验设计,深入了解AGEs-RAGE信号通路的作用机制,以期为糖尿病肾病的中西医结合治疗提供一定参考。

Diabetic nephropathy is a common clinical complication of diabetes mellitus.It is one of the main causes of end-stage renal disease and one of the important factors that cause death of diabetic patients.Advanced glycosylation end products(AGEs)-receptor of AGEs(RAGE)signaling pathway is an important link in the occurrence and development of diabetic nephropathy.The main mechanism of action in diabetic nephropathy is activating nuclear factor-κB(NF-κB),stimulating the production of vascular endothelial growth factor(VEGF),and stimulating transforming growth factor-β1(TGF-β1),inducing the expression of monocyte chemotactic protein-1(MCP-1),activating P21 renin-angiotensin to cause cell dysfunction,activating nicotinamide adenine dinucleotide phosphate(NADPH)oxidase to cause oxidative stress and so on.TCM treatment of diabetic nephropathy has the advantages of overall regulation,multi-channel and multi-target.It can improve the progress of diabetic nephropathy by blocking AGEs-RAGE signaling pathway.The main problems in current research are as follows:the downstream mechanism of AGEs-RAGE is complex and not fully elucidated.The relationship between AGEs-RAGE and some key factors such asNF-κB,VGEF,TGF-β1,MCP-1 gene needs further research to confirm;there are many clinical and animal experiments on the treatment of diabetic nephropathy with the active ingredients of single Chinese materia medica and compound Chinese materia medica,but there are few studies on AGEs-RAGE signaling pathway;most of the experiments are carried out in vitro,and the mechanism and target of action are not clear.In future research,we need to further improve the experimental design and understand the mechanism of AGEs-RAGE signaling pathway in order to provide some reference for the treatment of diabetic nephropathy with integrated Chinese and Western medicine.