炎症反应是导致脊髓二次损伤的关键因素。星胶细胞表达多种炎症因子受体，脊髓损伤后内源性促炎因子与其结合激活炎症反应。MIF是中枢神经系统中重要致炎因子，但其激活星胶细胞炎症反应机制尚不清楚。课题组前期研究发现，MIF/CD74信号轴调控星胶细胞胆固醇羟化酶CH25H的表达，其中间产物氧化型胆固醇25HC发挥致炎效应。因此课题组拟建立大鼠脊髓损伤模型，分析MIF和CH25H表达相关性，揭示MIF调控CH25H的细胞学基础；MIF刺激原代星胶细胞并结合基因敲降技术，分析CH25H、炎症因子和趋化因子表达及其机制；25HC处理星胶细胞和炎症细胞，研究其对细胞增殖迁移、炎症因子、趋化因子产生影响及其信号途径；在大鼠损伤脊髓中干预MIF或CH25H表达，检测对损伤脊髓炎症因子、趋化因子、轴突生长及动物行为学影响。通过MIF促进胆固醇氧化激活损伤脊髓炎症反应的机制研究，为脊髓损伤修复提供新思路和新靶点。

Excessive inflammation is one of key factors resulting in second tissue damages of traumatic spinal cord. Several endogenous proinflammatory cytokines are able to activate the inflammatory responses of astrocytes due to its expression of cytokine receptors. Both MIF and 25HC have been found to facilitating inflammation of microglia, but our previous works also reveal that MIF can upregulate CH25H expression to induce the inflammation of astrocytes. To clarify the underlying mechanisms, we are going to establish spinal cord injury model and analyze the expression changes of MIF and CH25H at the different times, as well as their colocalization with astrocytes and microglia, in an attempt to understand where the regulation occurs. Then, we will treat the primary cultured astrocytes with recombinant MIF with or without knockdown the expression of relative CH25H, to examine the protein levels of CH25H, inflammatory cytokines and chemokines, and the associated signaling. Next, we will stimulate astrocytes and microglia with 25HC, followed by detecting proliferation and migration of the cells, and protein levels of inflammatory cytokines and chemokines, as well as related signal pathway. At last, we try to interfere with the expression of MIF or CH25H in the injured spinal cord, and to analyze the contents of inflammatory cytokines and chemokines, followed by observation of axonal regrowth and animal behaviors. Based on the investigation of MIF facilitating inflammation of injured spinal cord by regulation of CH25H expression, we will provide new clues and novel target for spinal cord repair.