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

发布时间：2018-07-13 12:39

【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。
[Abstract]:Intestinal dysbacteriosis is one of the high risk factors for advanced chronic kidney disease (chronic kidney disease) to uremia, characterized by the reduction of probiotics and the production of urinary toxin (urease producing bacteria). The number of endotoxin producing bacteria and metabolic toxin producing bacteria were increased. " The core of the theory of "gut-kidney axis" and the concept of "chronic kidney disease-colon axis (chronic kidney disease-colonic axis)" suggests that the dysfunctional intestinal flora exacerbates renal damage by increasing the accumulation of urotoxin and inducing systemic microinflammation. Preliminary clinical and animal trials showed that probiotics represented by lactic acid bacteria and bifidobacterium, probiotics represented by chrysanthemum and galactose, and rubiprost, Activated carbon adsorbent can improve renal function by reducing accumulation of urinary toxin and inhibiting systemic microinflammation. Not only that, some oral or intestinal administration of single Chinese medicine, traditional Chinese medicine compound and traditional Chinese medicine extract (emodin and so on) can also regulate intestinal bacteria to some extent, protect intestinal epithelial barrier, reduce the accumulation of urotoxin, delay the progress of CKD. Among them, rhubarb meridian prescription-rhubarb Licorice decoction (concentrated granule TJ-84) can improve the accumulation of urinary toxin in animal model of renal failure not as kidney, but as "enterorenal axis initiated by intestinal flora". Therefore, the interventional study of intestinal microflora related to intestinal microflora (tight junction protein, helper T cells, etc.) may be one of the important development directions in the future.
【作者单位】：南京中医药大学中西医结合鼓楼临床医学院中医科;南京大学医学院附属鼓楼医院中医科;南京中医药大学附属医院肾内科;南京中医药大学第二临床医学院中医养生学教研室;Division
【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)
【分类号】：R692

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