CXCL12 通过激活 JAK/STAT 通路促进中枢神经系统髓鞘修复的机制研究

视神经脊髓炎（NMO）是一种致盲性中枢神经系统脱髓鞘疾病，约50%患者以视神经炎首发。本团队前期研究创新性发现CXCL12水平与NMO疾病及视神经髓鞘的修复再生有关，两篇相关文章已发表。本团队通过细胞实验表明CXCL12可明显促进少突胶质前体细胞（OPCs）的成熟分化；且我们改良了NMO动物模型构建方法，并证实补充CXCL12对中枢神经系统有明显保护作用。那么，CXCL12具体是如何促进髓鞘修复并保护的？Stem Cell杂志有文献表明JAK/STAT信号通路可被CXCL12激活并在神经细胞的分化过程中发挥了重要作用。因此我们提出假设，CXCL12可以通过激活JAK/STAT通路促进OPCs分化，使少突胶质细胞数量增加促使髓鞘修复。本课题拟通过体内和体外实验进一步验证该假说，从而揭示CXCL12促髓鞘修复的部分调控机制，为探索促髓鞘再生、提高患者视力预后的可能途径积累新的科学依据。

Neuromyelitis optica(NMO) is a blinding demyelinating disease in central nervous system. Approximately 50% patients attack with optic neuritis initially. Our team previously found that CXCL12 level was associated with NMO, affecting remyelination of optic nerve sheath, and the papers had been published. Our cell experiment showed that CXCL12 could promote differentiation and maturation of oligodendrocyte precursor cells(OPCs) prominently. And we improved the method of building NMO animal model, which indicated that supplement of CXCL12 could protect the central nervous system effectively. Thus, how did CXCL12 promote the remyelination and protect it specifically? Paper on Stem Cell magazine showed JAK/STAT signal pathway could be activated by CXCL12 and plays an important role in differentiation of nerve cell. Therefore we hypothesized that, CXCL12 could promote differentiation of OPCs by activating JAK/STAT signal pathway, and increase the number of oligodendroglia cells to promote the repair and regeneration of myelin sheath. Our research would further verify the hypothesis by observing in vivo and vitro, trying to reveal the mechanism partially and provide new scientific evidence to promote the remyelination and improve prognosis.