摘要
肠易激综合征(irritable bowel syndrome,IBS)是一种以慢性腹痛为主要症状,伴排便习惯改变的一种异质性疾病,其中腹泻型IBS(IBS-diarrhea,IBS-D)最为常见且影响最大。由于IBS的病理生理机制复杂,虽然该领域目前已有大量的相关研究,但其具体的发病机理仍不清楚。近年来,越来越多的研究发现,胆汁酸代谢异常和肠黏膜炎症在IBS-D的发生发展中具有重要作用。约25%的IBS-D患者存在胆汁酸代谢异常,表现为粪便中总胆汁酸增加,初级胆汁酸的比例升高,并且胆汁酸核受体法尼醇X受体(Farnesoid X receptor,FXR)表达及活性下降。一方面,FXR-FGF19信号通路下调引起胆汁酸合成增加,进而导致肠道中水和电解质分泌增加,结肠收缩增加,加重IBS-D。另一方面,由于FXR与NF-κB存在相互抑制作用,其表达及活性的下调减弱了对NF-κB的抑制,导致肠道炎症的反复与慢性化。本文就FXR与肠黏膜炎症在IBS-D发病机制中的作用作一概述。
Irritable bowel syndrome(IBS)is a heterogeneous disease,which includes chronic abdominal pain and changes in bowel habits.IBS-diarrhea(IBS-D)is generally reported as the most common subtype of IBS.Due to the complex pathophysiological mechanism of IBS,although a large number of related studies have been carried out in this field,its specific pathogenesis is still unclear.It is accepted that bile acid metabolism disorder and intestinal mucosal inflammation play an important role in pathophysiology of IBS-D in recent years.25%of patients with IBS-D have bile acid metabolism disorder,which is manifested as increased total bile acids in feces,increased proportion of primary bile acids,and decreased expression and activity of bile acid nuclear receptor Farnesoid X receptor(FXR).On the one hand,down-regulation of FXR-FGF19 signaling pathway leads to increased bile acid synthesis,which in turn leads to increased intestinal liquid and electrolyte secretion and colonic contraction,as a result of development of IBS-D.On the other hand,due to the mutual inhibitory effect of FXR and NF-κB,the down-regulation of its expression and activity weakened the inhibition of NF-κB result in the recurrence and chronicity of intestinal inflammation.This article reviewed the role of FXR and intestinal mucosal inflammation in the pathogenesis of IBS-D.
作者
王广祥
崔立红
董昌昊
冼锐
WANG Guangxiang;CUI Lihong;DONG Changhao;XIAN Rui(Department of Gastroenterology,the First Medical Center of Chinese PLA General Hospital,Beijing 100853;The Second School of Clinical Medicine,Southern Medical University,China)
出处
《胃肠病学和肝病学杂志》
CAS
2022年第11期1212-1218,共7页
Chinese Journal of Gastroenterology and Hepatology
基金
国家自然科学基金资助项目(8207032296)。
