术后认知功能障碍（POCD）是患者术后长期严重并发症之一，但发病机制不清、治疗手段缺乏。我们前期研究发现老年鼠POCD的易感性高于青年鼠，其血清同型半胱氨酸（Hcy）含量较高；老年鼠术后海马NR2B表达增强，NR2B甲基化水平降低；术前补充维生素B12可降低Hcy，逆转手术所致的NR2B甲基化水平降低，改善老年鼠POCD。由于Hcy可经蛋氨酸循环抑制DNA启动子甲基化、增强特定基因表达调控认知功能，且NR2B表达受甲基化调控，其过量表达可引发胞内钙超载损伤神经元，我们推测：高Hcy经蛋氨酸循环降低NR2B启动子甲基化水平、促进NR2B 蛋白表达，引发胞内钙超载，进而导致神经元损伤，造成老年鼠POCD。本课题拟通过腹腔探查术构建POCD模型，利用在体微透析、CHIP、电生理等技术，明确Hcy是否通过抑制NR2B甲基化调控POCD发生，为POCD的发病机制和临床防治提供新思路和新方法。

Postoperative cognitive dysfunction (POCD) is one of the long-term postoperative complications. The mechanism of POCD is unclear, lacking of the effective therapy. Our pilot study showed that elderly mice were more susceptible to POCD than young mice, the concentration of homocysteine (Hcy) in elderly mice was also higher; In the hippocampus of postoperative elderly mice, the expression of NR2B was enhanced and the methylation of NR2B promoter was decreased; Preoperative supplementation of vitamin B12 decreased the concentration of Hcy, reversed the postoperative reduction of NR2B methylation, and improved POCD in elderly mice. Previous studies have found that Hcy regulates cognitive function by inhibiting DNA methylation through methionine cycle and enhancing the expression of specific gene, in addition, the expression of NR2B can be regulated by methylation, NR2B overexpression results in calcium overload and subsequently leads to neuron damage. Based on this, we propose a hypothesis: elevated Hcy could inhibit the methylation of NR2B through methionine cycle, up-regulate NR2B expression and result in calcium overload, subsequently lead to neuron damage and produce POCD. The current study aims to investigate whether Hcy regulates POCD by inhibiting NR2B methylation, using in vivo microdialysis, CHIP and electrophysiology in animal POCD model established by abdominal exploration. This study is to provide a new idea for the mechanism research and a novel treatment for POCD in clinic.