术后认知功能障碍（POCD）是目前老年患者术后常见的中枢神经系统并发症，其发病机制不清，神经炎症在POCD的发生发展中发挥了中心环节作用。近年来研究表明表观遗传学尤其是DNA甲基化、组蛋白乙酰化在认知功能及炎症的调控作用日益受到重视，但其如何调控突触可塑性导致POCD的机制还不得而知。本课题利用不同年龄小鼠、培养不同时间的海马神经元或胶质细胞，异氟烷麻醉、或合并胫骨骨折手术模型，通过行为学、电生理、免疫荧光组织化学、免疫荧光细胞化学、免疫印迹、ChIP、RT-PCR、MSP、RNA干扰、病毒感染等方法，在分子、细胞和整体水平研究老龄DNA甲基化及组蛋白乙酰化异常参与麻醉手术所致炎症因子IL-1β生成、影响和突触可塑性相关蛋白EphB2表达，导致NMDA受体跨膜转运异常、突触可塑性受损而致认知功能障碍的机制，为POCD的发病及干预措施提供理论依据和治疗的新靶点。

Postoperative cognitive dysfunction (POCD) is a common complication of central nerve system in senior patients. The pathogenesis of POCD remains largely unknown, which makes it an important issue in the fields of Anesthesia and Neuroscience. Now it’s widely accepted that neuroinflammation plays a central role in the pathogenesis and development of POCD. Epigenetic modifications, especially the DNA methylation and histone acetylation play an important role in cognition and neuroinflammation. But it’s unknown whether and how it has a role in regulating the synaptic plasticity leading to the POCD. In this study, we will clarify the role and mechanisms for DNA methylation and histone acetylation in the IL-1β and EphB2 gene expression, which affect GluN2B-containing NMDA receptors trafficking, synaptic plasticity and cognition at molecular, cellular and behavioral levels by using isoflurane and fracture of tibia surgery models in young and old C57 mice, as well as hippocampal or glia cells cultures. Diverse methods such as behaviors, electrophysilology, immunohistochemistry, immunocytochemistry, western blots, CHIP, RT-PCR, MSP, RNA interference, viral infection et al., will be used. These will help us to understand the mechanisms for POCD and find new therapeutic targets.