肠道菌群与局部肾素-血管紧张素系统对糖尿病肾病的影响及中医药研究进展

Effects of Intestinal Flora and Local Renin-angiotensin System on Diabetic Nephropathy and Traditional Chinese Medicine Intervention:A Review

糖尿病肾病(DN)是临床常见的糖尿病并发症,是导致终末期肾脏病(ESRD)的主要原因,同时也是糖尿病患者生存的关键决定因素。糖尿病肾病发病机制复杂,目前认为与血流动力学异常、肠道菌群紊乱、糖脂代谢紊乱、氧化应激、遗传易感性及蛋白非酶糖基化等有关。局部肾素-血管紧张素系统(RAS)一直都是糖尿病肾病致病性和进行性变化的核心,其一旦被激活,会进而诱发血管内产生大量氧自由基,破坏内皮功能,影响机体微循环。随着最近的研究发现,肠道菌群及其代谢产物可能通过激活或者拮抗局部RAS从而影响DN的发生发展。中药治疗糖尿病肾病相比单纯西药治疗具有多靶点、不良反应小等优势。近年来不少中医学者发现单味药及其有效成分提取物、中药复方可以通过调节局部RAS或者调节肠道菌群的方式改善肾脏功能,如补脾的党参、山药、白术、茯苓,也有补肾的熟地黄、山茱萸、太子参;以及具有活血化瘀通络功效的水蛭、丹参、当归。该文整理并归纳了肠道菌群与局部RAS在DN的发生发展过程中起到的作用,并且参考近几年中药干预DN的动物实验或临床试验,进行分析、归纳,总结,以期为DN的中西医结合治疗提供更多的治疗策略和理论依据。

Diabetic nephropathy(DN)is a common clinical complication of diabetes,the main cause of end-stage renal disease(ESRD),and a key determinant of survival in diabetic patients.The pathogenesis of DN is complex,and it is currently believed to be associated with hemodynamic abnormalities,intestinal flora disturbances,glucose and lipid metabolism disorders,oxidative stress,genetic susceptibility,and protein non-enzymatic glycosylation.The local renin-angiotensin system(RAS)has always been the core of the pathogenic and progressive changes of DN.Once activated,it will induce the massive release of oxygen free radicals in the blood vessels,damage the endothelial function,and affect the microcirculation of the body.The recent studies demonstrate that intestinal flora and its metabolites may affect the occurrence and development of DN by activating or antagonizing the local RAS.Compared with western medicine treatment,traditional Chinese medicine(TCM)has the advantages of multiple targets and little toxic and side effects.Many TCM scholars have found that single herbs,their active ingredient extracts,and TCM compound prescriptions can improve kidney function by regulating the local RAS or intestinal flora.Specifically,the Chinese medicinal materials tonifying spleen(Codonopsis Radix,Dioscoreae Rhizoma,Atractylodis Macrocephalae Rhizoma,and Poria),replenishing kidney(Rehmanniae Radix Praeparata,Corni Fructus,and Pseudostellariae Radix),and activating blood,resolving stasis,and dredging collaterals(Hirudo,Salviae Miltiorrhizae Radix et Rhizoma,and Angelicae Sinensis Radix)have the regulatory effect.This article summarizes the roles of intestinal flora and local RAS in the occurrence and development of DN,and analyzes the animal experiments or clinical trials of TCM intervention in DN in recent years,aiming to provide more therapies and a theoretical basis for the treatment of DN with integrated TCM and Western medicine.