脊髓损伤后HMGB1蛋白激活炎症因子的释放及作用机理研究

项目名称： 脊髓损伤后HMGB1蛋白激活炎症因子的释放及作用机理研究

项目编号： No.81201434

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 陈克冰

作者单位： 中山大学

项目金额： 23万元

中文摘要： HMGB1能够加重大脑缺血性损伤后炎症反应，但它在脊髓损伤后的确切作用尚不明确。我们前期研究发现：脊髓损伤后早期HMGB1的表达上调，其释放早于TNF-α、IL-1β，它与受体RAGE结合诱导损伤后炎症反应。既往研究证实，HMGB1通过激活NF-κB信号通路，诱导单核/巨噬细胞释放TNF-α、IL-1β。因此，我们推测HMGB1可能作为上游炎症因子激活脊髓损伤后TNF-α、IL-1β的释放。本研究拟制备脊髓损伤体内和体外模型，通过给予HMGB1单克隆抗体或HMGB1 siRNA抑制脊髓损伤后HMGB1的表达，利用Western Blot、免疫组化和RT-PCR检测各组标本不同时间点HMGB1、TNF-α、IL-1β的蛋白及mRNA表达变化，验证HMGB1能够促进脊髓损伤后TNF-α、IL-1β的表达，并探讨HMGB1诱导炎症因子释放的机制，从而确立HMGB1在脊髓损伤后炎症反应中的重要地位

中文关键词： 高迁移率族蛋白B1；脊髓损伤；炎症因子；细胞迁移；

英文摘要： Recent studies demonstrated that the release of high-mobility group box 1 (HMGB1) stimulated the inflammatory reaction after brain ischemic injury. However, the role of HMGB1 as an inflammatory cytokine after spinal cord injury has not been studied in detail. In our previous study, HMGB1 expression in the injured spinal cord appeared at an earlier phase than that of TNF-α and IL-1β. HMGB1 and its receptors RAGE contributed to the inflammatory response after spinal cord injury. Recent studies confirmed that HMGB1 could induce tumor necrosis factor (TNF)-α and interleukin (IL)-1β synthesis and secretion in monocyte/macrophages via the activation of NF-κB pathway. Therefore, we speculate that HMGB1 is likely an upstream inflammatory cytokine involved in the regulation of TNF-α and IL-1β secretion after spinal cord injury. In the present study, we intend to perform in vivo and in vitro models of spinal cord injury, and administrate HMGB1 monoclonal antibody or HMGB1 small interfering RNAs (siRNA) to suppress HMGB1 expression after spinal cord injury. The protein and mRNA expression of HMGB1, TNF-α and IL-1β are supposed to be examined in the different time points after spinal cord injury using western blotting, real-time polymerase chain reaction (RT-PCR) and immunohistochemical analysis. The purpose of current stud

英文关键词： HMGB1；spinal card injury；proinflammatory factor；cell migration；