盐酸法舒地尔治疗实验性自身免疫性脑脊髓炎的潜能与抗炎作用  

Anti-inflammatory Effect of Fasudil in Treating Experimental Autoimmune Encephalomyelitis

作　　者：侯绍蔚[1,2] 刘岳婷[1,2] 郭敏芳[2] 刘春云[2] 李艳花[2] 孟建[2] 肖保国[3] 马存根[1,2] 

机构地区：[1]山西医科大学第一临床医学院神经内科,030001 [2]山西大同大学脑科学研究所,037009 [3]复旦大学神经病学研究所,200040

出　　处：《中国临床神经科学》2012年第2期126-134,共9页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金课题(编号:81070957)

摘　　要：目的:探讨盐酸法舒地尔对实验性自身免疫性脑脊髓炎(EAE)的治疗效果及机制。方法:雌性C57BL/6小鼠,随机分为EAE对照组、盐酸法舒地尔干预组和盐酸法舒地尔治疗组。采用髓鞘少突胶质细胞糖蛋白多肽诱导慢性EAE模型。干预和治疗分别在免疫后第3天和症状出现时予以腹腔注射盐酸法舒地尔,观察EAE模型小鼠体重变化和临床症状,进行苏木精-伊红和CD4+T细胞染色,同时检测磷酸化肌球蛋白磷酸酶(p-MYPT1)和核因子(NF-κB)。结果:盐酸法舒地尔可推迟并改善EAE小鼠症状,减轻中枢神经系统炎细胞浸润,抑制脊髓和脑p-MYPT1及脊髓NF-κB的表达。Aim： To explore the therapeutic potential of fasudil and its possible mechanism in experimental autoimmune encephalomyelitis（EAE） model.Methods： Female C57BL/6 mice were randomly divided into EAE group,fasudil intervention group and fasudil treatment group.EAE model was induced by MOG35-55 peptide.Fasudil was injected intraperitoneally at day 3 post-immunization or at onset of symptoms respectively.At day 28 after immunization,mice were sacrificed,brains and spinal cords were obtained for HE staining and CD4＋ T cell staining.Protein extracted from brains and spinal cords were collected for the measurement of p-MYPT1 and NF-κB by Western blot.Results： Fasudil delayed onset of EAE and improved clinical symptoms.Pathological examination reveals that fasudil declined the infiltration of inflammatory cells in spinal cords,accompanied by inhibition of p-MYPT1 in spinal cords.Further studies showed that fasudil inhibited the expression of inflammatory factor NF-κB,especially in spinal cords of mice treated with fasudil intervention.Conclusion： The administration of fasudil in EAE can significantly suppress clinical symptoms,which may be related to inhibition of inflammatory reaction and downregulation of p-MYPT1 and NF-κB.

关 键 词：盐酸法舒地尔 实验性自身免疫性脑脊髓炎 CD4+T细胞 磷酸化肌球蛋白磷酸酶 核因子 

分 类 号：R741[医药卫生—神经病学与精神病学] R744[医药卫生—临床医学]