从调控星形胶质细胞活化异质性探讨益肾化浊通络法对多发性硬化髓鞘再生适应性保护效应机制

Multiple Sclerosis (MS) is an inflammatory and demyelinating disease in the central nervous system and remyelination is an importantly endogenous repair mechanism that restores function of denuded axons in MS. There is now compelling evidence that the heterogeneity of reactive astrocytes (HRA) with the repair phenotype has the ability to promote remyelination, but HRA with the destructive phenotype inbibit remyelination. Preliminary studies indicate that Yishen Huazhuo Tongluo therapy (YHTT) has a trend of the ablity to protect myelin in MS. In this study, we are ready to explore the effects of YHTT on the localization and expression of the key protein, a “trigger point” protein in the bidirectional regulation (promote/inhibit) of remyelination of HRA, in the mouse model of MS by using appropriately detective methods. Based on this, we further to observe the effects of YHTT on the key target protein and gene expression in the different (promote/inhibit) pathways of HRA in the brain and spinal cord. Meanwhile, combined with observing the neurological function recovery in mouse model of MS and the microscopic morphology of astrocytes in the brain and spinal cord, we are ready to clarify the bidirectional regulation mechanism of HRA in MS, so as to provide preliminary experimental basis concerning the adaptively protective effect mechanism of Chinese medicine for remyelination.

多发性硬化（Multiple Sclerosis, MS）是一种中枢神经系统炎性脱髓鞘疾病，髓鞘再生对其神经功能恢复具有重要意义。研究显示，星形胶质细胞活化异质性（Heterogeneity of Reactive Astrocytes, HRA）在修复表型时对髓鞘再生有促进作用，但在破坏性表型时对其具有抑制作用。本研究在前期发现益肾化浊通络法对MS具有髓鞘保护作用趋势基础上，拟通过复制MS小鼠模型，以该法中药为干预手段，采用相应检测方法，观察该法对HRA双向调控（促进/抑制）关键“扳机点”蛋白定位表达影响；在此基础上，进一步观察该法对脑与脊髓中HRA促进与抑制髓鞘再生不同途径关键靶点蛋白与基因表达变化；同时结合观察MS小鼠神经功能恢复情况以及脑与脊髓中星形胶质细胞微观形态结构变化，阐明益肾化浊通络法对MS后HRA双向调控作用机制，为探索中医药对MS髓鞘再生适应性保护效应机制提供实验依据。

多发性硬化（Multiple Sclerosis, MS）是一种中枢神经系统炎性脱髓鞘疾病，髓鞘再生对其神经功能恢复具有重要意义。研究显示，星形胶质细胞活化异质性（Heterogeneity of Reactive Astrocytes, HRA）在修复表型时对髓鞘再生有促进作用，但在破坏性表型时对其具有抑制作用。本研究通过复制MS小鼠模型，以益肾化浊通络法中药为干预手段，采用相应检测方法，观察了该法对HRA双向调控（促进/抑制）关键“扳机点”蛋白Drd2及其下游Cryab蛋白定位表达影响，明确了该法对脑与脊髓中HRA促进（IL-6、IL11、CXCL1、LIF、BDNF、MCP-1、CNTF、IGF-1、NT-3）与抑制（NgR、CSPGs、EphA、FGF-2）髓鞘再生不同途径关键靶点蛋白表达变化；同时结合观察MS小鼠神经功能恢复情况以及脑与脊髓中星形胶质细胞微观形态结构变化，阐明了益肾化浊通络法对MS后HRA双向调控作用机制，为探索中医药对MS髓鞘再生适应性保护效应机制提供了实验依据。