氯马斯汀促进实验性自身免疫性脑脊髓炎小鼠的再髓鞘化  

Clemastine promotes remyelination in mice with experimental autoimmune encephalomyelitis

作　　者：孟仁亮 谢阳 张瑶 李作孝 MENG Ren-liang;XIE Yang;ZHANG Yao;LI Zuo-xiao(The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China)

机构地区：[1]西南医科大学附属医院

出　　处：《天津医药》2019年第8期819-823,共5页Tianjin Medical Journal

摘　　要：目的探讨氯马斯汀对实验性自身免疫性脑脊髓炎(EAE)小鼠髓鞘碱性蛋白(MBP)表达的影响。方法将50只C57BL/6雌性小鼠适应性喂养后按随机数字表法分成5组,即正常对照组、EAE模型组和氯马斯汀高、中、低剂量组[40、20、10mg/(kg·d)],每组10只。EAE模型组及氯马斯汀各剂量组采用抗原髓鞘少突胶质细胞糖蛋白35-55(MOG35-55)诱导EAE模型。氯马斯汀各剂量组每天腹腔注射氯马斯汀预防性给药,正常对照组和EAE模型组腹腔注射生理盐水,连续21d。建模后每天评判小鼠临床表现,进行神经功能障碍评分。21d后统一处死小鼠,观察各组小鼠脊髓组织病理切片的Luxol Fast Blue染色情况并进行脱髓鞘评分。观察各组小鼠脑组织匀浆中MBP及其mRNA表达的变化。结果正常对照组未发病。EAE模型组和氯马斯汀各剂量组从7~8d开始不同程度发病,在12~16d逐渐达到发病高峰,且随着干预剂量增大,小鼠发病高峰评分降低(P<0.01)。正常对照组小鼠脊髓组织未发生脱髓鞘改变;EAE模型组小鼠脊髓组织发生明显脱髓鞘改变;氯马斯汀各剂量组小鼠脱髓鞘程度明显改善,且改善程度呈剂量依赖性(P<0.01)。与正常对照组比较,EAE模型组与氯马斯汀各剂量组MBP蛋白及mRNA表达明显减少(P<0.05);与EAE模型组对比,氯马斯汀各剂量组MBP及其mRNA表达显著升高(P<0.05),呈剂量依赖性。结论氯马斯汀对MOG35-55诱导小鼠EAE模型具有防治作用,呈现剂量依赖性,其机制可能与促进MBP表达、改善再髓鞘化有关。Objective To investigate the effect of clemastine on the expression of myelin basic protein (MBP) in experimental autoimmune encephalomyelitis (EAE) model mice. Methods Fifty C57BL/6 female mice were randomly divided into five groups according to the random number table after adaptive feeding: normal group, EAE group and high, middle and low dose of clemastine[40, 20 and 10 mg/(kg·d)]intervention groups. There were 10 mice in each group. EAE models were induced by antigen myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) in EAE group and three clemastine intervention groups. The intervention groups received preventive administration of clemastine, while the normal group and EAE group received physiological saline by intraperitoneal injection continuously for 21 days. The clinical manifestations of the mice were evaluated daily after the model was established, and the neurological impairment scores were scored. The mice were sacrificed after 21 days. Luxol Fast Blue (LFB) staining and demyelination score were observed in pathological sections of spinal cord of each group. Changes of MBP and its mRNA expression in brain homogenate of mice were observed in five groups of mice. Results Mice in the normal group didn’t suffer from the disease. Mice of EAE group and clemastine intervention groups began to develop the disease in different degrees from the 7th to 8th d, and reached the peak from the 12th to 16th d. With the increase of intervention dosage, the peak score decreased (P<0.01). LFB staining showed that no demyelination changes in spinal cord in normal group. The significant demyelination in spinal cord was found in EAE group. Changes of the demyelination in spinal cord were significantly improved in three clemastine intervention groups, and the degree of improvement was dose-dependent (P<0.01). Compared with the normal group, the MBP and its mRNA expression were significantly decreased in EAE group and three clemastine interventions groups (P<0.05). Compared with the EAE group, the MBP and its mRNA expr

关 键 词：脑脊髓炎 自身免疫性 实验性 氯马斯汀 髓磷脂碱性蛋白质类 脱髓鞘 再髓鞘化 

分 类 号：R744.51[医药卫生—神经病学与精神病学]