慢性肾脏病肠道菌群失调的病理机制、治疗策略及中药的干预作用  

Pathomechanism and treatment of gut microbiota dysbiosis in chronic kidney disease and interventional effects of Chinese herbal medicine

作　　者：韩文贝 刘莹露[1] 万毅刚[2] 孙伟[3] 涂玥[4] 杨晶晶[1] 吴薇[1] 何伟明[3] 姚建 

机构地区：[1]南京中医药大学中西医结合鼓楼临床医学院中医科,江苏南京210008 [2]南京大学医学院附属鼓楼医院中医科,江苏南京210008 [3]南京中医药大学附属医院肾内科,江苏南京210029 [4]南京中医药大学第二临床医学院中医养生学教研室,江苏南京210023 [5]Division of Molecular Signaling,Department of Advanced Biomedical Research,Interdisciplinary Graduate School of Medicine and Engineering,University of Yamanashi

出　　处：《中国中药杂志》2017年第13期2425-2432,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81374030;81373604;81573903);国家自然科学基金青年科学基金项目(81603675);中央高校基本科研业务费专项资金项目(021414380219);江苏省自然科学基金青年科学基金项目(BK20161046);江苏省高校自然科学研究面上项目(16KJB360004)

摘　　要：肠道菌群失调是中、晚期慢性肾脏病(chronic kidney disease,CKD)进展至尿毒症的高危因素之一,其特征就是益生菌减少、能产生尿毒素的条件致病菌(产尿素酶菌群、产内毒素菌群以及产代谢毒素菌群)增多。"肠-肾轴(gut-kidney axis)"学说和"慢性肾脏病-结肠轴(chronic kidney disease-colonic axis)"概念的核心观点认为,失调的肠道菌群通过加剧尿毒素蓄积和诱导全身性微炎症反应等途径加重肾脏的损伤。初步的临床试验和动物实验的结果显示,以乳酸菌和双歧杆菌制剂为代表的益生菌和以菊粉、低聚半乳糖为代表的益生元,还有鲁比前列酮、活性炭吸附剂等都可以针对CKD患者体内失调的肠道菌群,通过减轻尿毒素蓄积和抑制全身性微炎症反应等途径而改善肾功能。不仅如此,一些经口服或肠道给药的单味中药、中药复方还有中药提取物(大黄素等)在一定程度上也能调节肠道细菌,保护肠道上皮屏障,减轻尿毒素蓄积,延缓CKD进展。其中,大黄类经方——大黄甘草汤(浓缩颗粒TJ-84)改善肾衰竭动物模型体内尿毒素蓄积的靶点不是肾脏,而可能是"肠道菌群所启动的肠-肾轴"。基于此,针对中、晚期CKD患者肠组织中肠道菌群相关的病理因素(紧密连接蛋白、辅助性和调节性T细胞等)的干预性研究可能是今后的重点发展方向之一。The gut microbiota dysbiosis is one of the risk factors in the progression from the advanced chronic kidney disease（CKD）to uremia,characterized by the reduction of probiotics and the increase of opportunistic pathogens including urease-related microbes,endotoxin-related microbes and toxin-related microbes,which can produce uremic toxins. According to the core point of ＂ the gut-kidney axis＂ theory and ＂ the chronic kidney disease-colonic axis＂ concept,the gut microbiota dysbiosis aggravates renal damage by accumulating uremic toxins and inducing the systemic micro-inflammation. The preliminary clinical trials and animal experiments show that the probiotics biologicals fromLactobacillus acidophilus or Bifidobacterium,and the prebiotics including inulin and galactooligosaccharides,as well as lubiprostone and activated carbon adsorbents can be used for improving dysfunction of CKD patients with the gut microbiota dysbiosis via reducing uremic toxins and inhibiting the systemic micro-inflammation. But not only that,it is reported that,to some extent,a number of the single Chinese herbal medicine（ CHM）,the CHM prescriptions and the CHM extracts（ emodin,etc.） with oral or enema administration can also regulate the gut microbiota dysbiosis,protect the intestinal epithelial barrier,reduce uremic toxins accumulation and delay CKD progression. Thereinto,Dahuang Gancao Decoction（ the concentrated granule TJ-84）,a classical CHM prescription of rhubarb,can ameliorate uremic toxins accumulation in the animal models with renal failure probably through targeting the gut-kidney axis triggered from gut microbiota,but not targeting the kidney. Based on these results,the interventional studies targeting the gut microbiota-related pathological factors such as tight junction proteins,helper T cells and regulatory T cells in the intestinal tract of the advanced CKD patients will become one of the key development directions in the future.

关 键 词：肠道菌群 中药 慢性肾脏病 肠-肾轴 病理机制 

分 类 号：R692[医药卫生—泌尿科学]