neuritin抑制神经炎症改善糖尿病中枢神经病变的作用机制研究

项目名称： neuritin抑制神经炎症改善糖尿病中枢神经病变的作用机制研究

项目编号： No.81471040

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 周吉银

作者单位： 中国人民解放军第三军医大学

项目金额： 73万元

中文摘要： 我们前期研究证明恢复糖尿病大鼠脑组织中neuritin水平可改善中枢神经病变。但其作用机制尚未阐明。新近实验证实，neuritin可抑制TRAF6/NF-κB信号通路拮抗脂多糖诱导的小胶质细胞炎症反应。推测neuritin可能通过调控该信号通路改善糖尿病中枢神经病变。本项目拟构建脑组织特异性高表达neuritin的转基因大鼠和特异性敲除neuritin小鼠，在体分析脑组织高表达和敲除neuritin对糖尿病中枢神经病变和炎症反应的影响；体外使用neuritin刺激小胶质细胞和小胶质细胞与神经细胞共培养，采用Western blotting、real-time PCR、EMSA等技术分析neuritin通过TRAF6/NF-κB信号通路对小胶质细胞活化的影响。本项目将为neuritin调控小胶质细胞炎症信号通路以抑制神经炎症反应来改善糖尿病中枢神经病变提供实验依据。

中文关键词： neuritin；糖尿病中枢神经病变；神经炎症；小胶质细胞

英文摘要： Our being studied NSFC project showed that reversing the down-regulated neuritin expression in brain improved central neuropathy of diabetic rats. But the protective mechanism of neuritin on diabetic central neuropathy is still unclear. Our recent studies showed that neuritin suppressed TRAF6/NF-κB signaling pathway to inhibit lipopolysaccharide-induced microglial inflammation. So we speculate: neuritin regulates TRAF6/NF-κB signaling pathway to improve diabetic central neuropathy. In the project, we will construct lentiviral expression vectors of neuritin and mice with brain-specific knockout neuritin, and analyze the impact of overexpression and knockout of neuritin in brain on diabetic central neuropathy and neuroinflammation in vivo; the technologies, such as Western blotting, real-time PCR and EMSA, are used to investigate the effect of neuritin on microglia activation through TRAF6/NF-κB signaling pathway in microglia-neuron coculture. This project will provide experimental basis that neuritin regulates signaling pathway of microglial inflammation to inhibit neuroinflammation and to improve diabetic central neuropathy.

英文关键词： neuritin;diabetic central neuropathy;neuroinflammation;microglia