阿托伐他汀对EAE模型髓鞘再生调节的机制研究  

The effect of atorvastatin on remyelination in experimental autoimmune encephalomyelitis

作　　者：陈丽萍[1] 张静[1] 李振飞[1] 单明月 宋秀娟[1] 檀国军[1] 李彬[1] 董梅[1] 郭力[1] 

机构地区：[1]河北医科大学第二医院神经内科,河北省神经病学重点实验室,石家庄050000

出　　处：《脑与神经疾病杂志》2015年第1期5-9,共5页Journal of Brain and Nervous Diseases

基　　金：国家自然青年基金项目(81100884);河北省卫生厅课题(20130506)

摘　　要：目的观察阿托伐他汀对实验性自身免疫性脑脊髓炎(EAE)小鼠髓鞘再生的作用,并研究相关机制。方法建立C57BL/6小鼠EAE模型,免疫成功后给予阿托伐他汀干预。应用Knoz评分观察小鼠的临床评分,免疫组化法观察IL-17浸润情况。体外培养少突胶质祖细胞(OPCs),观察其IL-17受体的表达。分别应用IL-17、阿托伐他汀及阿托伐他汀+甲羟戊酸内酯干预OPCs的培养及分化。结果阿托伐他汀可以减少EAE模型中IL-17在中枢神经系统的浸润。体外研究表明,OPCs表达IL-17受体,IL-17可增强OPCs表达p38 MAPK,从而抑制其增殖和分化;阿托伐他汀可以降低OPCs细胞p38 MAPK的表达,促进细胞的增殖;而甲羟戊酸内酯又可以部分逆转阿托伐他汀的作用。结论 OPCs表达IL-17受体,IL-17可以抑制髓鞘再生。阿托伐他汀可能通过Rho-p38 MAPK通路调控IL-17的表达,进而减轻EAE的髓鞘损伤,有助于髓鞘再生。Objective To observe the effect on remyelination of atorvastatin in the treatment of experimental autoimmune encephalomyelitis （EAE）.Methods EAE was induced in C57BL/6 mice.Atorvastatin was administered orally. Immunohistochemistry for IL-17 was performed to assess IL-17 positive cells in the infiltrates. OPCs were cultured in vitro. IL-17 receptor expression in OPCs were detected. IL-17, atorvastatin and mevalonolactone were added into OPCs culture medium as intervents.Results Atorvastatin prevented clinical and histologic experimental autoimmune encephalomyelitis （EAE）. Atorvastatin attenuated the infiltration of inflammatory IL-17 cells in EAE. OPCs constitutively express IL-17R. IL-17 can upgrade the express of p38 MAPK on OPCs, and the ability of cell proliferation, differentiation was suppressed by IL-17. Atorvastatin reduced p38 MAPK activation of OPCs by Western blot. Atorvastatin-induced effects were reversed by co-treatment with mevalonolactone. Conclusion Our results demonstrate that the remyelination can be suppressed by IL-17.The inhibition of Rho family functions in OPCs by atorvastatin promotes myelin repair in ameliorating EAE.

关 键 词：阿托伐他汀 实验性自身免疫性脑脊髓炎 多发性硬化 髓鞘再生 P38丝裂原活化蛋白激酶 

分 类 号：R744.5[医药卫生—神经病学与精神病学]