CD200-CD200R信号通路作为术后认知功能障碍关键治疗靶点的实验研究

Postoperative cognitive dysfunction (POCD) is one of serious neurological complications during perioperative period. Previous studies indicate that activated microglia and neuro-inflammation is involved in POCD. It has been demonstrated that CD200-CD200R may play an important role in the activation of microglia in neurodegenerative brain through immunomodulation. Therefore, we speculated that CD200R agonist (CD200Fc) could be used for the treatment of POCD. For validating the hypotheses, we will use cell culture, electrophysiology, Western blot, immunofluorescence, ELISA to examine the action of CD200Fc on POCD. We also will investigate the underlying mechanisms, such as activation pattern of microglia, immunomodulation, amyloid protein metabolism and synaptic morphology. The proposal provides a new promising way for the treatment of POCD.

术后认知功能障碍（POCD）是围术期严重并发症，目前认为与小胶质细胞激活和神经炎症有关。研究表明，CD200-CD200R信号通路与神经退行性疾病脑内小胶质细胞激活有关，发挥着免疫调节作用。我们推测：手术创伤可以引起海马区CD200-CD200R表达下降，引起海马区小胶质细胞有害M1样激活增加，有害炎症因子表达增加；神经保护性的M2样激活减少，保护性炎症因子表达减少，从而引起实验鼠空间和记忆能力的损害；CD200Fc可以转换该局面，治疗老年大鼠POCD。为验证此假说， 我们将采取细胞培养、神经电生理、免疫印迹、免疫荧光、ELISA、Golgi染色等技术和方法，在整体动物、细胞和脑片三个水平，从功能、形态和行为三个角度，研究CD200Fc治疗POCD可行性，从小胶质细胞激活方式、免疫调节、淀粉样蛋白代谢和突触形态和功能方面研究其机制，为治疗POCD提供了一个有前途的解决方案。