let-7b在肠黏膜对克罗恩病相关粘附性侵袭性大肠杆菌免疫应答中的作用

项目名称： let-7b在肠黏膜对克罗恩病相关粘附性侵袭性大肠杆菌免疫应答中的作用

项目编号： No.81500429

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 郭振

作者单位： 中国人民解放军东部战区总医院

项目金额： 18万元

中文摘要： 肠道菌群与肠黏膜间的相互作用是克罗恩病（CD）发病机制的重要组成部分。研究证实，microRNAs可以介导二者间的相互作用，在克罗恩病发病中扮演着重要角色。CD相关粘附性侵袭性大肠杆菌（AIEC）主要定植于CD患者末端回肠，被认为是CD发病的始动和持续因素之一，AIEC对microRNA的调控参与其作用机制。我们前期研究发现let-7b在CD回肠黏膜中的表达水平与 AIEC存在相关性，且其作用靶点TLR-4是AIEC引起肠道炎症的重要通路之一。我们推测CD相关 AIEC可以通过抑制let-7b上调TLR-4水平，导致TLR-4通路异常活化，引起肠道炎症。在前期研究工作基础上，本课题拟以CD模型小鼠及人肠上皮细胞为研究对象，利用免疫组化、分子生物学等技术，通过AIEC感染和调控let-7b表达，探讨let-7b在CD相关AIEC诱导肠黏膜炎症中的作用，以期为CD治疗提供新的靶点。

中文关键词： 克罗恩病；微小RNA；粘附性侵袭性大肠杆菌；Toll样受体-4；肠道炎症

英文摘要： The interactions between gut microbiota and intestinal mucosa play a key role in the pathogenesis of Crohn's disease(CD). Increasing evidences demonstrated microRNAs which could mediate microbiota - mucosa interactions are pivotal in CD. CD-associated adherent invasive Escherichia coli (AIEC) are mainly present in the ileum of CD patients, and have been implicated as a causative agent or contributory factor in disease pathology. Some studies showed AIEC could regulate the expression of microRNAs. Our previously study found the expression of let-7b in the ileal mucosa of CD patients was correlated with the abundance of AIEC, and TLR-4 which is an important pathway of inflammation associated with AIEC is one target of let-7b. Therefore, we hypothesize that AIEC could up-regulate TLR-4 by depressing the expression of let-7b, and then result in excessive inflammation in the intestinal mucosa. Hence, we proposed a study focused on the AIEC and let-7b in CD mouse model and human intestinal epithelial cells ,performed in vivo and vitro, by molecular biology and immuno technology techniques. Furthermore, by infection with AIEC and regulation of let-7b,the effects of let-7b on the intestinal inflammation caused by AIEC will also be explored. The result of our study may add some information for the understanding of the pathogenesis of CD and provide some therapeutic implications for the treatment of CD.

英文关键词： Crohn’ Disease;microRNA;adherent-invasive E coli;Toll-like receptor-4;intestinal inflammation