基于肠道紧密连接的细胞旁通透性研究进展

Advances on Paracellular Permeability Based on Intestinal Tight Junctions

肠上皮细胞紧密连接作为肠道屏障的重要组成部分,不仅决定肠道的细胞旁通透性,还在维护肠道内环境稳定、防止有害物质侵入等方面发挥重要作用。当紧密连接的结构或功能受损时,肠道屏障的完整性遭到破坏,导致细胞旁通透性显著增加,细菌、内毒素、病毒及大分子物质便可通过细胞旁路途径进入组织和器官,从而引起肠道疾病发生。但是不同分子通过肠道紧密连接的途径也不同,目前证明主要有两种细胞旁路途径,即孔隙途径和渗漏途径。这两种途径在分子大小、通透性及调控机制方面有所不同,孔隙途径主要涉及小分子物质通过,通过调节紧密连接蛋白Claudin-2的表达影响孔隙途径通透性,进而影响肠道屏障功能;而渗漏途径主要涉及大分子物质通过,Occludin、Tricellulin、ZO-1等紧密连接蛋白在这一途径中发挥关键作用,以维护肠道屏障的完整性。笔者以影响孔隙途径和渗漏途径通透性的相关蛋白为出发点,阐明这些蛋白影响孔隙途径和渗漏途径通透性的调控机制,从而防止有毒有害物质进入体内,以期为肠上皮紧密连接屏障破坏引起肠道疾病的防治提供理论依据。

As an important component of the intestinal barrier,the intestinal epithelial cell tight junction not only determines the paracellular permeability of the intestinal tract,but also plays an important role in maintaining the stability of the intestinal environment and preventing the invasion of harmful substances.When the structure or function of the tight junctions is damaged,the integrity of the intestinal barrier is disrupted,resulting in a significant increase in paracellular permeability,bacteria,endotoxins,viruses and macromolecules can enter tissues and organs through the paracellular pathway,leading to the occurrence of intestinal diseases.However,different molecules have different ways to pass through the intestinal tight junctions,and there are two primary paracellular pathways,the pore pathway and the leak pathway.These two pathways are different in terms of molecular size,permeability and regulatory mechanisms.The pore pathway mainly involves the passage of small molecules,and regulating the expression of tight junction protein Claudin-2 affects the permeability of the pore pathway,which in turn affects the function of the intestinal barrier.Whereas the leak pathway mainly involves the passage of large molecules,and tight junction proteins,such as Occludin,Tricellulin and ZO-1,play a key role in this pathway.Occludin,Tricellulin,ZO-1 and other tight junction proteins play a key role in this pathway to maintain the integrity of the intestinal barrier.Taking the relevant proteins affecting the permeability of the pore pathway and the leak pathway as the starting point,the author elucidated the regulatory mechanisms of these proteins affecting the permeability of the pore pathway and the leak pathway,thus preventing the entry of toxic and harmful substances into the body,with a view to provide theoretical basis for the prevention and treatment of intestinal diseases caused by the disruption of the intestinal epithelial tight junction barrier.