术后肠麻痹(postoperative ileus，POI)临床常见，部分严重者常出现各种并发症，其机制不明，成为临床预防和治疗的重点和难点。课题组前期研究提示，手术引发的炎症反应及肠黏膜通透性增高是POI的主要发病学环节。本项目聚焦于“术后肠麻痹-肠屏障异常/肠黏膜通透性变化-肠道细菌/内毒素移位-炎症反应-加重术后肠麻痹”这一可能的因果连锁反应，采用C57BL小鼠野生型和TLR4、JNK基因敲除型，通过在体和离体动物实验，动态观测POI小鼠肠屏障功能，尤其肠黏膜通透性、肠道菌群、肠道相关淋巴组织（GALT）及免疫功能的变化, 揭示肠屏障功能紊乱在POI发病中的作用和可能的机制；通过比较不同类型小鼠胃肠运动紊乱、肠黏膜通透性改变、炎症反应等方面的特点，明确肠屏障改变引发/促进POI可能涉及的信号通路及其作用。研究将为进一步阐明POI的发病机制提供客观依据，为POI的临床防治提供新的思路。

Postoperative ileus (POI) is a clinically common ailment. Although some cases are mild with a benign finale, serious paralytic ileus may occur in severe cases, causing a variety of complications. With mechanism still being elusive, these cases are intricate and resistant to clinical intervention; hence the call for special attention, funding and investigation. Our privious study showed that the inflammation and high permeability in the intestinal mucosa are involved in the development of POI. In this project, by using POI model in C57BL mice（wild type,and TLR4-/-、JNK -/- types）, focusing the study on the possible cause and effect chain “the Postoperative ileus-Abnormal gut barrier and intestinal mucosal permeability-Translocation of the intestinal bacteria/ endotoxin-Inflammation-Aggravation of the postoperative ileus”, we plan to investigate the intestinal barrier function, in particular, the changes in intestinal permeability, alterations in intestinal flora and in gut-associated lymphoid tissue (GALT),and their roles and the related mechanisms in the progress of postoperative ileus, by in vivo and animal isolated-organ experiments. Moreover, the characteristics of gastrointestinal motility disorders, inflammatory reactions, and intestinal barrier malfunctions in the POI models of different mice will be compared, then the possible signal transduction pathways that may be involved in POI progression will be analyzed. The purpose of the proposed project is to make further efforts to elucidate the pathogenesis of POI and its related factors, as well as to provoke further clues for the development of new prevention and therapeutic strategies of POI.