低剂量白介素2对实验性自身免疫性脑脊髓炎小鼠的治疗效果研究  

Therapeutic effect of low dose interleukin-2 on experimental autoimmune encephalomyelitis in mice

作　　者：王震 段海峰 樊心童 许春阳 李金凤[4] 王姗姗 王运良[4] 吴祖泽 WANG Zhen;DUAN Hai-feng;FAN Xin-tong;XU Chun-yang;LI Jin-feng;WANG Shan-shan;WANG Yun-liang;WU Chu-tse(Weifang Medical University, Weifang,Shandong 261021 ,China;Institute of Radiation Medicine,Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China;Pingdingshan First People＇ s Hospital, Pingdingsan, Henan 467000, China;Department of Neurology, No. 148 Hospital of PLA, Zibo, Shandong 255300, China)

机构地区：[1]潍坊医学院,山东潍坊261021 [2]军事科学院军事医学研究院辐射医学研究所,北京100850 [3]平顶山第一人民医院,河南平顶山467000 [4]解放军148医院神经内科,山东淄博255300

出　　处：《军事医学》2017年第12期968-972,977,共6页Military Medical Sciences

基　　金：河南省科技发展计划资助项目(162102310557)

摘　　要：目的探讨白细胞介素2(IL-2)对实验性自身免疫性脑脊髓炎(EAE)小鼠的治疗效果。方法用髓鞘少突胶质细胞糖蛋白35-55(MOG35-55)多肽诱导建立EAE小鼠模型后,将小鼠分为对照组、EAE组、低剂量IL-2治疗组。每日对所有小鼠进行神经功能缺损评分。第29天取小鼠脑和脊髓行病理观察,HE染色进行炎性细胞浸润评分和髓磷脂染色(LFB)进行脱髓鞘评分;采用流式细胞仪技术检测调节性T细胞(Treg)和自然杀伤细胞(NK)比例;免疫组化法检测神经胶质原纤维酸性蛋白(GFAP)和碱性髓鞘蛋白(MBP)的表达。结果与EAE组相比,低剂量IL-2治疗组小鼠神经功能评分、脊髓炎性细胞浸润评分和脱髓鞘评分降低,而Treg细胞比例显著增加,且NK细胞轻度增加;免疫组化结果显示,低剂量IL-2治疗组小鼠GFAP蛋白表达量较模型组下降,而MBP蛋白表达量明显高于模型组。结论低剂量IL-2对EAE小鼠有显著治疗效果。Objective To investigate the therapeutic effect of interleukin-2 （IL-2） on experimental autoimmune encephalomyelitis （EAE） mice. Methods After establishment of the EAE （ experimental autoimmune encephalomyelitis） mouse models with MOG35-55 polypeptides, the mice were grouped according to the neurological function score and divided into control group, EAE group and low dose IL-2 treatment group. A double blind method was used to evaluate the neuro- logical impairment in mice. On the 29th day, pathological experiments were carried out in the mice＇s brain and spinal cord, hematoxylin-eosin staining was used to evaluate the scoring of inflammatory cell infiltration and luxol fast blue staining was used to evaluate the scoring of demyelinating. The proportion of regulatory T cells（Treg） and NK cells（ natural killer cell, NK ） was detected by flow cytometry, and the immunohistochemical method was used to detect the expressions of glial fibril- lary acidic protein （GFAP） and myelin basic protein （MBP） in the spinal cord. Results Compared with the EAE group, the neurological function score, the inflammatory cell infiltration score and the demyelinating score of the low dose IL-2 treatment group were reduced. The proportion of Treg cells in the low dose IL-2 treatment group was significantly higher than that in the EAE group, and the proportion of NK ceils in the low dose IL-2 treatment group was slightly higher than that in the EAE group The expression of GFAP and MBP was detected by immunohistochemistry. The expression level of GFAP in low dose IL-2 treatment group was significantly lower than that in the EAE group, while the expression level of MBP was higher than that in the EAE group. Conclusion Low dose IL-2 has significant therapeutic effect on EAE mice.

关 键 词：多发性硬化 脑脊髓炎 自身免疫性 实验性 调节性T细胞 白细胞介素2 神经胶质原纤维酸性蛋白 髓磷脂碱性蛋白质类 

分 类 号：R744.51[医药卫生—神经病学与精神病学]