关键词: 肠易激综合征, 同型半胱氨酸, 肠道屏障功能, 内脏敏感性, 紧密连接蛋白

Abstract: Objective To investigate the role of homocysteine (Hcy) in the pathogenesis of irritable bowel syndrome (IBS) and its effects on intestinal motility, visceral hypersensitivity, and barrier function. Methods Clinical cohorts and animal models were combined for this study. Clinically, fifteen IBS patients meeting Rome Ⅲ criteria and 15 control individuals were enrolled to detect fecal Hcy levels and their correlation with symptoms. As for animal experiments, water avoidance stress (WAS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) chemical induction were utilized to establish IBS rat and mouse models, combined with a high-methionine diet (HMD) to simulate hyperhomocysteinemia. IBS symptoms were evaluated through fecal water content, carmine red intestinal transit time,and visceral hypersensitivity scores. Immune-fluorescence and Western blot were used to detect intestinal epithelial tight junction proteins. Serum and fecal Hcy concentrations were measured to assess Hcy levels. Statistical analyses included t-tests and One-way Anova. Results Fecal Hcy level in IBS patients were significantly higher than those in the healthy control group which demonstrated a positive correlation with defecation frequency(P＜0.01). In animal models, the combination of TNBS administration and a high-methionine diet markedly elevated serum and fecal Hcy levels in mice, while synergistically exacerbated intestinal motility disorders and visceral hypersensitivity. In vitro experiments showed that Hcy treatment down-regulates the expression of tight junction proteins in human colon cancer cell line(Caco-2). Conclusions Hcy plays an important role in the pathogenesis of IBS by impairing intestinal barrier function and enhancing visceral hypersensitivity, and it may serve as a potential new target for the treatment of IBS.

Key words: irritable bowel syndrome, homocysteine, intestinal barrier function, visceral hypersensitivity, tight junction protein