中文摘要：

目的探索新型Rho激酶抑制剂FSD-C11化合物治疗实验性自身免疫性脑脊髓炎（EAE）的有效性及可能的作用机制,为今后可能的临床治疗提供实验依据。方法采用小鼠髓鞘少突胶质细胞糖蛋白35-55（MOG35-55）多肽诱导雌性C57BL/6小鼠建立EAE模型,于免疫后第3天起FSD-C11组按体质量40mg/（kg·d）腹腔注射FSD-C11化合物,EAE组注射等量生理盐水,实验期间每天定时记录两组小鼠临床症状评分及体质量变化。免疫后第28天取小鼠脊髓进行HE和髓鞘染色,流式细胞术检测脾细胞M1和M2型巨噬细胞表型,Western blot检测脑组织中诱导型一氧化氮合酶（iNOS）和磷酸化核蛋白因子κB（p-NF-κB）的表达。结果FSD-C11化合物可延迟小鼠的起病时间,降低发病率,减轻临床症状,减少体质量丢失;与EAE组小鼠相比,FSD-C11可减少脊髓炎性细胞浸润和髓鞘脱失（P〈0.05）;抑制致炎性的M1型巨噬细胞,增加抗炎性和保护性的M2型巨噬细胞;抑制脑组织中iNOS和p-NF-κB蛋白的表达。结论新型Rho激酶抑制剂FSD-C11化合物在治疗EAE中显现出很好的潜力,其作用机制可能与调节巨噬细胞极性、抑制炎性反应有关。

英文摘要：

Objective We observed the therapeutic effect of FSD - Cll and its mechanisms in experimental autoimmune encephalomyelitis （EAE）. FSD - Cll is a novel Rho kinase inhibitor that is derived from Fasudil hydrochloride. Methods Chronic EAE was induced by myelin oligodendrocyte glycoprotein peptides 35-55 （MOG35-55） in female C57BL/6 mice. FSD-C11 compound was injected intraperitoneally at 40 mg/ （kg· d） from day 3 post-immunization （p. i） to day 27 p. i, and physiological saline was injected in control group. Clinical symptoms and body weight of mice were recorded on time every day. On day 28 p. i, the mice were sacrificed and spinal cords were obtained for HE and myelin staining. Splenocytes were separated, CD16/32 and CD206 were detected by flow eytometry. Protein extracting from brain was collected to detect the expression of nitric oxide synthase （iNOS） and nueleoprotein factor p-NF-κB by western blot. Results FSD-C11 ameliorated the clinical severity of EAE, decreased the incidence of disease, and reduced the loss of body weight. Compared with the control group, FSD-C11 reduced the spinal inflammatory cell number and demyelination （P〈0.05）. Macrophages in the FSD-C11 group shifted M1 to M2 phenotype. FSD-C11 group showed decreased inflammatory responses, increased anti-inflammatory responses, and inhibited expression of iNOS and p-NF-κB in the brain.Conclusions FSD-C11, as a novel Rho kinase inhibitor, exhibited therapeutic potential in EAE. Its mechanism may be related to regulating macrophages polarity and inhibit inflammatory reaction.