基于TLR5通路介导的小肠上皮细胞相关肠道免疫屏障损伤在非甾体抗炎药肠病肠道菌群移位中的作用及云母干预研究

肠道通透性增高、肠道菌群移位、肠源性内毒素血症是非甾体抗炎药（NSAIDs）肠病发生出血、穿孔等多重恶性循环的重要因素，其机理为肠道机械及免疫屏障功能障碍。前期研究研究发现云母可修复NSAIDs肠病小肠上皮细胞（IECs）并能通过IECs的Toll样受体-5（TLR5）激活参与肠道局部免疫及细菌分布的调节，具体机制有待进一步阐明。故课题组拟在NSAIDs肠病伴发肠道细菌移位的小鼠模型平台上，运用条件性基因敲除（TLR5f/f）技术、体外共刺激诱导淋巴细胞分化以及生物荧光标记细菌示踪等技术进一步明确IECs及其TLR5信号系统直接和/或间接通路调控NSAIDs肠病肠道免疫屏障、细菌移位及云母的干预机制，不但有助于揭示NSAIDs肠病具体分子机制，更有可能为开发以IECs为靶标的新型免疫治疗提供理论依据，为中医药治疗NSAIDs肠病提供新思路。

Increased intestinal permeability, bacterial translocation and enterogenous endotoxemia are the important factors of multiple vicious cycles such as hemorrhage and perforation in intestinal diseases caused by Non-steroidal anti-inflammatory drugs (NSAIDs), the mechanism of which is intestinal mechanical and immune barrier dysfunction. In previous studies, mica was found to be able to repair intestinal epithelial cells (IECs) of NSAIDs enteropathy and participate in the regulation of intestinal local immunity and bacterial distribution through the activation of Toll like receptor-5 (TLR5) of IECs. The specific mechanism needs to be further elucidated. Therefore, the research team plans to use conditional gene knockout (TLR5 f/f) technology, technique of inducing lymphocyte differentiation by co-stimulation in vitro and bioluminescence labeled bacteria tracing technology to further clarify that IECs and TLR5 signaling system directly and / or indirectly regulate the intestinal immune barrier, bacterial translocation and intervention mechanism of mica of NSAIDs enteropathy on the mice model platform of NSAIDs enteropathy with intestinal bacterial translocation. This will not only help to reveal the specific mechanism of NSAIDs enteropathy, but also provide theoretical basis for the development of new immunotherapy targeting IECs, and provide new ideas for the treatment of NSAIDs enteropathy with traditional Chinese medicine.