R.hominis促进PMP22表达修复肠黏膜屏障减轻肠易激综合征内脏高敏感的机制研究

肠黏膜屏障受损是肠易激综合征（IBS）患者发病的关键环节，肠黏膜附着菌群对维持屏障完整性具有重要作用。我们的前期研究发现肠道共生菌R.hominis可逆转应激所致内脏高敏感，并促进肠黏膜紧密连接蛋白（TJPs）表达，但具体机制尚不清楚。我们的预实验发现R.hominis及其鞭毛蛋白可促进肠黏膜TLR5和周围髓鞘蛋白（PMP22）的表达。鉴于PMP22对肠黏膜屏障的保护作用，我们推测R.hominis通过激活肠上皮TLR5上调PMP22表达，从而促进TJPs的稳定性。本项目将通过建立细胞与动物模型，应用免疫荧光、分子生物学等技术，证实PMP22参与R.hominis对肠黏膜屏障的保护作用，并对IBS患者肠黏膜标本中R.hominis丰度、PMP22表达及其与症状的相关性进行探讨。研究结果将为通过修复肠黏膜屏障治疗IBS提供实验依据，有助于发掘罗斯氏菌在临床中的使用价值，具有重要的转化意义。

The damage of intestinal mucosal barrier plays a key role in the pathogenesis of irritable bowel syndrome (IBS), and the microbiota adherent to intestinal mucosa are essential to maintain the integrity of the barrier. Our previous study found that R. hominis could reverse the stress-induced visceral hypersensitivity and promote the expression of tight junction proteins (TJPs), but the specific mechanisms are still unclear. Our preliminary study found that R. hominis and its flagellin could promote the expression of TLR5 and peripheral myelin protein 22 (PMP22) in the intestinal mucosa. In view of the protective effect of PMP22 on intestinal mucosa barrier, we speculate that R. hominis can maintain the stability of TJPs by activating TLR5 in intestinal epithelium and upregulating the expression of PMP22. In this project, we will establish cellular and animal models to confirm that PMP22 participates in the protective effect of R. hominis on intestinal mucosal barrier by using immunofluorescence staining and molecular biology and other technologies, and to further investigate the abundance of R. hominis and the expression of PMP22 in intestinal mucosa of IBS patients and their correlation with symptoms through clinical specimens. The results will provide experimental basis for the treatment of IBS through the repairment of intestinal mucosal barrier, and contribute to explore the clinical value of R. hominis, which has translational medical significance.