认知功能障碍是术后常见的中枢神经系统并发症，伴有社会活动能力减退，严重影响患者预后，其患病机制之一是手术创伤诱发的中枢神经炎症。本课题组前期研究证实，IL-6是外周创伤诱导中枢神经炎症和认知功能障碍的必要和充分条件，同时伴有中枢内sIL-6R表达增加和小胶质细胞活化，提示IL-6/sIL-6R信号通路和小胶质细胞的激活可能是外周创伤诱导中枢炎症和认知功能障碍的重要途径。基于大量的前期工作，提出以下假设：IL-6通过IL-6/sIL-6R信号通路刺激小胶质细胞向M1型极化，参与介导神经元损伤，从而诱导神经炎症和认知功能下降。本项目将运用小鼠在体去小胶质细胞、小胶质细胞和海马神经元共培养等技术，在外周创伤和IL-6诱导的小鼠认知功能障碍模型上，系统阐述IL-6通过IL-6/sIL-6R信号通路激活小胶质细胞诱导神经炎症发生的细胞分子机制，为临床防治措施的改进和新药物的研发提供神经物学依据。

Post-operative Cognitive Decline is a common postoperative complication accompanied by diminished social activities, and seriously influences the recovery of patients. An important mechanism underlying such morbidity is the neuroinflammation caused by surgical trauma. Our team confirmed that cytokine IL-6 is a necessary and sufficient condition for peripheral trauma-induced central inflammation and cognitive decline with increased expression of sIL-6R in the central nervous system and activation of microglia, suggesting the IL-6/sIL-6R signaling pathway and microglial activation may be essential for peripheral trauma-induced neuroinflammation and Cognitive Decline. Based on a large number of previous studies, our group proposed the following hypothesis: IL-6 activates microglia to M1-like polarization through IL-6/sIL-6R signaling pathway and is involved in mediating neuronal damage and thus neuroinflammation. Using the models of peripheral trauma and IL-6-induced Cognitive Decline, we will systematically elucidate the molecular mechanism of microglial activation and neuroinflammation mediated by IL-6/sIL-6R signaling pathway exploit with the techniques of in vivo microglia elimination and co-culture of microglia and hippocampal neurons, and so on. This study will provide the neurobiological basis for the improvement of clinical therapeutic measures and the development of new drugs.