从调控星形胶质细胞活化TNFR2/CXCL12/CXCR4通路探讨益肾化浊通络法对多发性硬化髓鞘再生的保护效应机制

Multiple Sclerosis (MS) is an inflammatory and demyelinating disease in the central nervous system. Remyelination plays an important role in the nerve function recovery of MS. There is now compelling evidence that the TNFR2/CXCL12/CXCR4 pathway induced by the reactive astrocytes has the ability to promote remyelination or 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 the TNFR2/CXCL12/CXCR4 pathway induced by the reactive astrocytes, 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 in the different(promote/inhibit) pathways of the TNFR2/CXCL12/CXCR4 pathway induced by the reactive astrocytes 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 regulation mechanism of the TNFR2/CXCL12/CXCR4 pathway induced by the reactive astrocytes 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，髓鞘再生是其神经功能恢复关键因素。研究显示，星形胶质细胞活化TNFR2/CXCL12/CXCR4通路对髓鞘再生具有促进/抑制双重作用。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，观察该法对星形胶质细胞活化TNFR2/CXCL12/CXCR4通路双向调控（促进/抑制）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星形胶质细胞活化TNFR2/CXCL12/CXCR4通路促进与抑制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，阐明益肾化浊通络法对MS后星形胶质细胞活化TNFR2/CXCL12/CXCR4通路调控髓鞘再生的作用机制.

多发性硬化（Multiple Sclerosis, MS）是一种中枢神经系统炎性脱髓鞘疾病，髓鞘再生是其神经功能恢复关键因素。研究显示，星形胶质细胞活化TNFR2/CXCL12/CXCR4通路对髓鞘再生具有促进/抑制双重作用。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，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，结果表明益肾化浊通络法具有延缓EAE 起病时间、减轻疾病严重程度，各个时间点的脊髓组织炎性细胞浸润、髓鞘脱失及轴索变性程度较EAE 组明显减轻。在此基础上，进一步观察该法对脑与脊髓中星形胶质细胞活化TNFR2/CXCL12/CXCR4通路促进与抑制髓鞘再生不同途径关键靶点蛋白表达变化；免疫后，EAE组JAK2、STAT3、P-STAT3、JAK3、STAT5、P-STAT5、Rac1Cdc42、PAK1、RhoA、Rock2、CXCL12、CXCR4 较正常对照组明显差异; 免疫后各时间点，益肾化浊通络法较模型组均明显差异，这个结果初步阐明益肾化浊通络法对MS后星形胶质细胞活化TNFR2/CXCL12/CXCR4 通路双向调控作用机制，为探索益肾化浊通络法对MS 髓鞘再生适应性保护效应机制提供初步实验依据。