补阳还五汤干预EAE气滞血瘀证神经保护的多位点作用研究

项目名称： 补阳还五汤干预EAE气滞血瘀证神经保护的多位点作用研究

项目编号： No.81473577

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 马存根

作者单位： 山西中医药大学

项目金额： 72万元

中文摘要： 临床研究表明，补阳还五汤能有效缓解MS病情，减少发作次数与发作程度。现代药理发现，补阳还五汤中的部分药物及有效成分可以选择性地降低炎性细胞因子含量，减轻自由基损伤，增加MS动物模型实验性自身免疫性脑脊髓炎（EAE）炎性细胞凋亡，减轻神经组织损伤，从而保护神经细胞。Rho/Rho激酶（ROCK）信号通路的激活与MS/EAE的发生、发展密切相关，抑制ROCK信号通路的激活已成为神经系统炎性变性疾病很有希望的治疗策略。因此，本研究拟在免疫后诱导期（第3天）和免疫后发病期（第14天），给予补阳还五汤干预，观察补阳还五汤治疗EAE气滞血瘀证的临床评分、髓鞘修复能力、外周和中枢免疫调节效应、血脑屏障（BBB）的完整性及神经再生等神经保护作用的效果，以及调控ROCK/TLR4/NF-κB的细胞分子机制，阐明中药复方治疗MS的靶点与途径，对指导临床运用益气活血法有效防治MS有重要的理论意义和实用价值。

中文关键词： 补阳还五汤；益气活血法；实验性自身免疫性脑脊髓炎；神经保护；Rho/ROCK信号

英文摘要： Clinical studies have shown that Buyang Huanwu decoction had a therapeutic effect in ameoliorating the severity of multiple sclerosis(MS), reducing the number of relapses. Modern pharmacological studies reveal some active ingredients of Buyang Huanwu decoction exerts neuroprotective effects by decreasing inflammatory cells and inflammatory cytokines,inhibiting the damage of free radical. Rho-kinase (ROCK),a serine/threonine kinase,is activated in experimental autoimmune encephalomyelitis (EAE). The blockade of Rho/ROCK is considered to be beneficial to achieving neuroprotection, axonal regeneration, oligodendrocyte generation, and suppressing inflammatory responses. Thus, targeting ROCK inhibition is a promising strategy to treat central nervous system (CNS) disease. We induced a chronic- progressive EAE with Qi Deficiency and Blood Stable Syndrome in B6 mice immunized with myelin oligodendrocyte glycoprotein35-55 and intervent it with Buyang Huanwu decoction in early and late stages of the disease. The goal of this investigation is to further explore the efficacy of peripheral and CNS immunomodulatory and inflammatory responses, includig regulation of T cell subsets, polarization of macrophage subsets, investigate the integrity of blood brain barrier(BBB)and regeneration. We try to expore the expression and activation of ROCK/ TLR-4/ NF-κB, attempt to pay close attention to multi-targets for the neuroprotection and neuroregeneration of MS/EAE. These studies will expand the therapeutic strategies of Yiqihuoxue Method for treatment of MS/EAE.

英文关键词： Buyang Huanwu decoction;Yiqihuoxue Method;experimental autoimmune encephalomyelitis;neuroprotection;Rho/ROCK signalling pathway