中文摘要：

目的探讨Rho激酶抑制剂Fasudil衍生物FSD—C11治疗实验性自身免疫性脑脊髓炎（EAE）的免疫调节机制。方法采用MOG35-55多肽建立C57BL／6小鼠EAE模型，随机分为FSD—C11组和Saline组，于免疫后第3天起腹腔注射FSD—C11化合物和Saline。免疫后28d处死小鼠，FACS法检测脾组织CD4＋T细胞亚群，ELISA法检测外周免疫系统中细胞因子的分泌情况，Western blot法测定脊髓ROCKⅡ、iNOS、Arg-1、TLR-2和TLR-4的蛋白表达。结果FSD—C11干预EAE能够抑制脊髓中ROCKⅡ表达，减少外周CD4＋IFN-γT细胞，增加CD4＋IL-10＋和CD4＋CD25＋T细胞（P〈0．05），减少外周免疫系统炎性细胞因子IFN-1、IL-17、IL-6、IL-1β和TNF-α的含量（P〈0．05），而增加IL-10的含量（P〈0．05），抑制脊髓组织中巨噬细胞标志蛋白iNOS表达、增加Arg-1的表达（P〈0．05）。抑制脊髓组织中TLR-2和TLR-4蛋白表达（P〈O．05）。结论FSD—C11可调节外周免疫细胞活化和增殖，抑制外周免疫系统分泌炎性因子，增加保护性的细胞因子，改善炎性微环境，促进M1型巨噬细胞向M2型转化，控制CNS的炎性细胞侵润，从而达到减轻或改善EAE的临床症状。

英文摘要：

This study aimed to investigate the mechanisms of novel Fasudil derivative FSD-Cll in the treatment of experimental autoimmune encephalomyelitis （EAE）. Chronic EAE model was induced by MOG35-55 peptides in female C57BL/6 mice. FSD-Cll or physiological saline were injected intraperitoneally from day 3 post-immunization to day 27 post-immunization. On day 28 post-immunization, mice were sacrificed and spinal cords were obtained for Western blot. Splenocytes were separated, and CD4＋T cell subset were detected by flow cytometry. The levels of cytokine were analyzed by ELISA. Data showed that the administration of FSD-Cll inhibited the expression of ROCK II in spinal cords, decreased CD4＋IFN-γ＋ T cells, increased CD4＋IL-10＋T cells and CD4＋CD25＋T cells in the peripheral immune system, and inhibited inflammatory cytokines IFN-γ IL-17, IL-6, IL-Iβ and TNF-α, but enhanced IL-10 level. Furthermore, FSD-Cll also inhibited the expression of macrophages phenotypic protein iNOS, up-regulated Arg-1 expression, inhibited the expression of TLR-2 and TLR-4 in spinal cords. Taken together, the therapeutic effect of FSD-Cll on EAE may relate to adjustment of peripheral immune cell activation and proliferation, such as inhibiting inflammatory cytokine and enhancing anti-inflammatory cytokine, improving inflammatory microenvironment, shifting M1 to M2 macrophages, preventing inflammatory cells migration into CNS.