IL-1β激活ROS/JNK通路参与术后肠麻痹发生及高脂肠内营养治疗的机制研究

The mechanism of postoperative ileus (POI) remains unknown, and there are few effective interventions for POI. In previous studies, we established an animal model for POI, and based on this, we found that intestinal inflammation is a major cause of POI and high-fat enteral nutrition (EN) could reduce intestinal inflammation and improve POI, but its mechanism is unclear. Recent studies and pre-experiment have shown that interleukin-1β (IL-1β) plays a key role in intestinal inflammation-induced POI, and IL-1β may finally induce organ dysfunction via c-Jun N-terminal kinase (JNK) signaling pathway activated by inducing a number of reactive oxygen species (ROS). Therefore, we suppose that surgical stress could induce intestinal IL-1β release, and lead to ROS production, and further result in the activation of JNK signaling pathway, which is an important mechanism of POI (IL-1β-activated ROS/JNK signaling pathway). In this study, to verify this hypothesis, we will perform experiments to specifically inhibit the expression of key proteins or molecules in this pathway in vivo and in vitro, and utilize many detection techniques such as laser scanning confocal microscope, flow cytometer and western blot. Firstly, we will fully explore the role of IL-1β-activated ROS/JNK signaling pathway in POI, and then explore whether high-fat EN could inhibit this pathway so as to improve POI. This study will provide a new strategy to prevent POI.

术后肠麻痹（POI）的发生机制目前仍不清楚，更缺乏有效防治手段。我们前期在成功建立POI动物模型基础上研究发现，肠道炎症是POI发生的主要原因，高脂肠内营养（EN）能降低术后肠道炎症，改善POI，但机制不明。新近研究及预实验显示，IL-1β是肠道炎症导致POI的关键，且IL-1β可能会通过促使活性氧族（ROS）大量产生来触发JNK信号通路，最终引发器官功能紊乱。因此，我们推测，手术应激引起肠道IL-1β释放将触发ROS活化，激活JNK信号通路，从而引起POI，即IL-1β介导的ROS/JNK信号通路激活假说。本课题拟采用体内外实验，通过特异性抑制该通路中关键蛋白或分子的表达，利用激光共聚焦显微镜、流式细胞仪和Western blot等，首先阐明IL-1β介导的ROS/JNK信号通路激活在POI中的作用，然后探讨高脂EN是否通过抑制该通路来改善POI，以期为临床防治POI提供新的思路和方案。

术后肠麻痹（POI）是外科术后常见且主要的并发症，严重影响患者的术后康复。然而POI的发生机制目前仍不清楚，更缺乏有效防治手段。我们前期在成功建立POI动物模型基础上研究发现，肠道炎症是POI发生的主要原因，高脂肠内营养（EN）能降低术后肠道炎症，改善POI，但机制不明。新近研究及预实验显示，IL-1β是肠道炎症导致POI的关键，且IL-1β可能会通过促使活性氧族（ROS）大量产生来触发JNK信号通路，最终引发器官功能紊乱。因此，我们推测，手术应激引起肠道IL-1β释放将触发ROS活化，激活JNK信号通路，从而引起POI，即IL-1β介导的ROS/JNK信号通路激活假说。本项目通过体内外实验的系统研究，阐明了IL-1β介导ROS/JNK信号通路激活参与POI发生，明确了高脂EN通过抑制该通路来改善POI。本项目的完成为临床防治POI提供新的思路和方案。