基于肠上皮黏膜屏障探讨功能性消化不良发病机制研究

Study on the Pathogenesis of Functional Dyspepsia Based on Intestinal Epithelial Barrier

功能性消化不良(functional dyspepsia,FD)是最常见的功能性上消化道疾病,主要分为餐后窘迫综合征(PDS)和上腹痛综合征(EPS)两个亚型。目前,FD的发病机制尚未完全阐明。而十二指肠上皮黏膜屏障作为物理肠道屏障最关键的组成部分,其损伤与FD的发病机制密切相关。十二指肠上皮黏膜屏障的损伤以紧密连接损坏为主,当紧密连接发生损伤时,紧密连接蛋白表达降低,肠道通透性增强,细菌、病原体、毒素等腔内物质通过“不受限制的”途径穿透肠上皮黏膜屏障,激活肠上皮黏膜免疫系统,十二指肠嗜酸性粒细胞和肥大细胞浸润增加,导致十二指肠低度炎症和组织损伤持续产生。这些低度炎症不仅可与上皮黏膜屏障损伤相互影响,还可进一步使十二指肠上皮黏膜下神经元的结构和功能发生异常,引发十二指肠神经感觉-运动功能障碍,导致FD症状的产生,为FD发病机制的研究提供新方向。文章从肠上皮黏膜屏障的结构功能以及与免疫和神经系统的相互作用出发,探讨肠上皮黏膜屏障损伤作用于FD的发病机制,为临床治疗和基础研究提供潜在的研究思路。

Functional dyspepsia(FD)is the most common functional upper gastrointestinal disease,which is mainly divided into two subtypes:postprandial distress syndrome(PDS)and epigastric pain syndrome(EPS).At present,the pathogenesis of FD has not been fully elucidated.As the most important part of physical intestinal barrier,the injury of duodenal epithelial mucosal barrier is closely related to the pathogenesis of FD.The injury of duodenal epithelial mucosal barrier is mainly tight junction damage,when tight junction injury occurs,the expression of tight junction protein decreases and intestinal permeability increases.Bacteria,pathogens,toxins and other lumen substances penetrate the intestinal epithelial mucosal barrier through an“unrestricted”pathway,activate the intestinal epithelial mucosal immune system,and increase the infiltration of eosinophils and mast cells in the duodenum.It leads to low-grade inflammation and tissue damage of the duodenum.These low-grade inflammation can not only interact with the injury of epithelial mucosal barrier,but also further abnormal the structure and function of duodenal submucosal neurons,cause sensory-motor dysfunction of duodenal nerve,and lead to FD symptoms,which provides a new direction for the study of the pathogenesis of FD.Based on the structure and function of intestinal epithelial mucosal barrier and its interaction with immunity and nervous system,this paper discusses the mechanism of intestinal epithelial mucosal barrier injury on the pathogenesis of FD,and provides potential research ideas for clinical treatment and basic research.