多发性硬化（MS）是一种中枢神经系统（CNS）炎性脱髓鞘疾病，髓鞘再生是其治疗的关键环节。前期研究证实，地黄活性成分梓醇可以重构调节性T细胞（Treg）在淋巴亚群中的分布，促进少突胶质细胞前体细胞（OPC）增殖、迁移与髓鞘再生，但是其作用的分子机制尚不明确。研究发现，调节性T细胞（Treg）能够分泌免疫分子CCN3，是髓鞘再生的重要环节。基于此，本项目采用EAE小鼠模型，结合OPC与神经元共培养模型，以免疫分子CCN3为第一信使，以细胞分裂控制蛋白（CDC）42为切入点，检测细胞内传导因子鸟苷酸交换因子（GEFs）与miR148b-3p对CDC42的协同作用，分析CDC42下游靶蛋白及基因，深入探讨梓醇促OPC增殖、迁移及轴突再髓鞘化的分子调控机制。本研究不仅可以诠释梓醇促轴突再髓鞘化的分子机制，也可以揭示补肾药物-地黄治疗CNS脱髓鞘的科学内涵，为解决轴突再髓鞘化这一关键环节提供新思路。

Multiple sclerosis (MS) is a central nervous system (CNS) inflammatory demyelinating disease. Remyelination plays a key step in the treatment of MS. Previous studies had confirmed that Catalpol, a component of rehmannia, could reconstitute the distribution of regulatory T cells (Treg) in lymphoid subpopulations. And Catalpol could promote the proliferation and differentiation of oligodendrocyte precursor cells (OPC) to remyelination. However, the molecular mechanisms are still unclear. Studies have found that Treg could secrete CCN3, one immune molecule which could promote remyelination. Based on this, the project adopts the EAE mice model combining with OPC and neuron co-culture, taking the immune molecule CCN3 as the first messenger to unveil the cell division control protein (CDC) 42 roles playing in remyelination. This study is to unveil the synergistic effect of guanine-nucleotide exchange factors (GEFs) and miR148b-3p on CDC42. The downstream target proteins and genes of CDC42 will be also detected. This study will unveil the molecular regulation mechanisms of Catalpol on promoting OPC proliferation, migration and remyelination. This study can not only explain the molecular mechanisms of Catalpol on remyelination, but also reveal the scientific connotation of CNS demyelination with tonifying kidney treatment. And this study will provide a new insight for remyelination.