Department of Neurology, Medical School, Institute of Brain Science, Shanxi Datong University, Datong, China.
CNS Neurosci Ther. 2012 Nov;18(11):909-17. doi: 10.1111/cns.12002. Epub 2012 Sep 21.
The purpose of this investigation was to further explore the mechanism(s) underlying the amelioration in EAE caused by Fasudil, particularly focusing on anti-inflammatory effect.
We induced a chronic-progressive experimental autoimmune encephalomyelitis (EAE) in B6 mice immunized with myelin oligodendrocyte glycoprotein(35-55) and performed Fasudil intervention in early and late stages of the disease.
The administration of Fasudil (40 mg/kg, i.p) had a therapeutic effect in delaying the onset and ameliorating the severity of EAE, accompanied by the improvement in myelination and the decrease in inflammatory cells in spinal cords. Fasudil inhibited TLR-4, p-NF-kB/p65, and inflammatory cytokines (IL-1β, IL-6, and TNF-α) and enhanced IL-10 production in spinal cords. The ratio of arginase/iNOS was enhanced mainly in the spinal cords of EAE mice treated with Fasudil, reflecting a shift toward the M2 (antiinflammation) macrophage/microglia phenotype. The administration of Fasudil also induced the upregulation of CB2 receptor in spinal cords, but did not significantly trigger CB1 receptor. Levels of neurotrophic factors NGF, BDNF, and GDNF in the CNS were not altered by Fasudil.
Fasudil ameliorates disease progression in EAE, acting possibly through antiinflammatory pathway.
本研究旨在进一步探讨法舒地尔改善实验性自身免疫性脑脊髓炎（EAE）的机制，特别是关注其抗炎作用。
我们在 B6 小鼠中诱导慢性进行性实验性自身免疫性脑脊髓炎（EAE），用髓鞘少突胶质糖蛋白（35-55）免疫，并在疾病的早期和晚期进行法舒地尔干预。
法舒地尔（40mg/kg，腹腔注射）的给药具有延迟发病和改善 EAE 严重程度的治疗作用，同时伴有髓鞘改善和脊髓中炎症细胞减少。法舒地尔抑制 TLR-4、p-NF-kB/p65 和炎症细胞因子（IL-1β、IL-6 和 TNF-α），并增加脊髓中 IL-10 的产生。法舒地尔治疗的 EAE 小鼠脊髓中主要增强精氨酸酶/iNOS 比值，反映向 M2（抗炎）巨噬细胞/小胶质细胞表型的转变。法舒地尔的给药还诱导脊髓中 CB2 受体的上调，但对 CB1 受体没有明显触发作用。法舒地尔不改变中枢神经系统中神经营养因子 NGF、BDNF 和 GDNF 的水平。
法舒地尔改善 EAE 的疾病进展，可能通过抗炎途径发挥作用。
