二甲双胍抑制Th17细胞反应对实验性自身免疫性脑脊髓炎小鼠保护作用  

Metformin alleviates the severity of experimental autoimmune encephalomyelitis by supressing T helper 17 response in mice

作　　者：孙雅菲[1] 马征[2] 侯慧清[1] 田甜[3] 陈丽萍[1] 王梁[1] 郭力[1] Sun Yafei;Ma Zheng;Hou Huiqing;Tian Tian;Chen Liping;Wang Liang(Department of Neurology,the Second Hospital of Hebei Medical University,Shijiazhang 050000,China)

机构地区：[1]河北医科大学第二医院神经内科,石家庄050000 [2]承德医学院附属医院神经内科 [3]承德医学院附属医院神经外科

出　　处：《脑与神经疾病杂志》2019年第1期15-19,共5页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金资助(81701186;81471228);2018年度河北省医学科学研究重点课题资助(20180352; 201502012)

摘　　要：目的探讨实验性自身免疫性脑脊髓炎(EAE)小鼠应用二甲双胍(MET)干预,观察MET对EAE小鼠发病情况、神经功能评分的影响及其对小鼠体内Th17细胞反应的作用。方法以MOG35-55免疫雌性C57BL/6小鼠建立EAE模型。随机分成对照组、EAE组和MET治疗组,比较不同组小鼠神经功能评分。在发病高峰期,比较小鼠脊髓中炎性细胞浸润程度,脾细胞中Th17细胞比例,脾细胞培养上清及血清中IL-17A含量以及小鼠脾及脊髓中IL-17A、RORγt mRNA转录水平。结果与EAE组相比,MET治疗组发病率减低(P<0.05),疾病严重程度减轻(P<0.01);脾细胞中Th17细胞比例降低(P<0.01),脾细胞培养上清及血清中IL-17A含量减少(P<0.01);脾及脊髓组织中IL-17A、RORγt mRNA转录水平均降低(P<0.01)。结论 MET通过抑制外周免疫器官及中枢神经系统的Th17细胞反应而对EAE小鼠起到保护作用。Objective To investigate the preventive effect of metformin on experimental autoimmune encephalomyelitis(EAE)mice,and explore the probable mechanism.Method The mice were randomly divided into control group,EAE group and metformin(MET)treatment group,and immunized with MOG35-55.The morbidity of disease and clinical signs were observed.The inflammatory cells in the central nerves system by HE were detected.The different percents of Th17 cells and concentrations of IL-17A in supernatants and serum were explored.RORγt,IL-17A mRNA transcripts in spleen and in spinal cord were detected in each groups.Results The clinical scores of mice in treatment group were lower than in EAE mice.There were many inflammatory cells in the EAE mice compared with the treatment group.The percentage of Th17 cells was higher in EAE mice than in treatment mice(P<0.01).The concentration of IL-17A in supernatants and serum in EAE group is higher than them in treatment mice(P<0.01).IL-17A and RORγt mRNA levels in the spleen and the spinal cord were enhanced in EAE compared with healthy mice,and the levels were reduced by MET treatment(P<0.01).Conclusion Metformin attenuates severity of EAE by supressing Th17 response in peripheral immune organ as well as in central nervous system.

关 键 词：二甲双胍 实验性自身免疫性脑脊髓炎 TH17细胞 RORΓT IL-17A 

分 类 号：R744.53[医药卫生—神经病学与精神病学]