多发性硬化症（MS）是常见的一种以中枢神经脱髓鞘为特征的自身免疫性疾病，实验性自身免疫性脑脊髓炎（EAE）是MS的理想动物模型。课题组前期研究发现EAE小鼠大脑白质胆固醇合成下调，复发缓解型MS患者适量补充固醇类物质有利于缓解病情。哺乳动物雷帕霉素靶蛋白（mTOR）激酶活性与胆固醇介导的髓鞘基因表达有关，但其参与EAE髓鞘修复的具体机制还未完全阐明。鉴于此，本研究拟首先建立EAE小鼠模型，探讨外源性胆固醇补充对髓鞘形成、运动功能及mTOR激酶活性的影响。进一步以原代少突胶质细胞（OLs）为研究对象，体外层面分析外源性胆固醇补充对OLs增殖分化成熟的影响，并且通过RNA干扰和免疫共沉淀等技术研究Ragulator-Rag-mTOR信号通路参与髓鞘修复功能的具体机制。本项目的实施将有助于完善外源性胆固醇影响MS的分子机制，也为MS髓鞘修复治疗提供新的方向，具有重要的理论意义和应用价值。

Multiple sclerosis (MS) is the most common autoimmune disease characterized by demyelination of the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is an ideal animal model for MS. Our previous studies have found that the synthesis of white matter cholesterol in the brain of EAE mice was down-regulated. In addition, for patients with relapsing-remitting MS, appropriate steroid supplement was beneficial to the remission of the disease. Mammalian rapamycin target protein (mTOR) kinase activity is related to cholesterol-mediated myelin gene expression, but the mechanism involved in EAE myelin repair has not been fully elucidated. Therefore, this study will be designed to establish an EAE mouse model to explore the effects of exogenous cholesterol supplementation on myelination, motor function and mTOR kinase activities. Moreover, we further discuss the effects of exogenous cholesterol supplementation on the proliferation, differentiation and maturation of oligodendrocytls (OLs), togehter with the the specific mechanism of Ragulator-Rag-mTOR pathway participated in myelin repair function through RNA interference and immunoprecipitation. The implementation of this project is not only helpful to improve the molecular mechanism of exogenous cholesterol affecting MS, abut also provide a new direction for myelin repair therapy, with theoretical significance and application value.