实验性自身免疫性脑脊髓炎小鼠模型的建立及其病理学和影像学表现.doc

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1、实验性自身免疫性脑脊髓炎小鼠模型的建立及其病理学和影像学表现作者：胡晓，袁军，万兴，娄磊，王建怡【摘要】目的：建立实验性自身免疫性脑脊髓炎(experimentalautoimmuneencephalomyelitis，EAE)小鼠模型并做病理学及影像学鉴定，为研究多发性硬化的发病机制奠定基础。方法：C57BL/6雌性小鼠80只，分为EAE1组、EAE2组、EAE3组、EAE4组，各15只，用MOG35-55抗原加完全弗氏佐剂不同注射方法制作EAE小鼠模型；佐剂组10只用生理盐水代替MOG3555制备免疫乳剂，对照组10只仅注射生理盐水；用MRI对小鼠脑和脊髓进行扫描，HE、

2、LFB染色和Bielschowskys银染观察小鼠脑和脊髓病理学改变。结果：免疫后第14天，EAE1组、EAE2组、EAE3组、EAE4组小鼠开始出现EAE临床症状，发病率分别为80%、80%、73%、67%；EAE2组、EAE3组小鼠临床症状评分与EAE1组比较，P＞0.05，EAE4组小鼠临床症状评分与EAE1组比较，P＜0.05；佐剂组与对照组小鼠均未出现临床神经系统症状；EAE小鼠脑和脊髓小血管周围炎细胞浸润呈袖套状或脱髓鞘改变，神经元变性及轴突损伤，MRI可显示脑和脊髓病灶。结论：应用背部、颈部、腋窝、蹊部多点注射可提高EAE发病率，1次免疫与两次免疫小鼠对EAE发病

3、率的影响没有明显差别。【关键词】脑脊髓炎；脑；脊髓；神经元；磁共振成像；小鼠　　［Abstract］Objective:Toestablishautoimmuneencephalomyelitis(AE)mousemodelandobserveitspathologicalandimagingappearance,andsoastoprovideabasisforstudyofpathologicalmechanismandtherapyofmultiplesclerosis.Methods:EightyC57BL/6femalemiceweredividedrandomlyi

4、nto6groups,with15ineachofgroupsofEAE1,EAE2,EAE3,andEAE4.Experimentalautoimmuneencephalomyelitis(EAE)wereinducedinmiceofthe4groupswith300μgofMOG35-55pluscompleteFreund'sadjuvant(CFA)bydifferentmethods.Miceinadjuvantgroup(groupADJ,n=10)weretreatedwithCFAplusnormalsaline,whilemiceincontrolgroup

5、(groupCON,n=10)treatedwithnormalsalineonly.MRIexaminationandpathologicalobservationonthebrainandspinalcordwerecarriedoutonmiceingroupsofEAE1,ADJ,andCON.MethodsusedinpathologicalobservationincludedHEstaining,LuxolFastBluestaining,andBieschowskysilverstaining.Results:ClinicalsymptomsofEAEappea

6、redinmiceofgroupsEAE1,EAE2,EAE3,andEAE4in14daysafterimmunization,andtheincidenceswere80%,80%,73%,and67%respectively.ClinicalsymptomscoresofgroupsEAE2andEAE3werenotstatisticallydifferentfromthatofgroupEAE1(P＞0.05),whilethatofgroupEAE4hadstatisticallysignificantdifferencefromthatofgroupEAE1(P＜

7、0.05).NoobviousEAEsymptomwasfoundingroupsADJor6CON.Pathologicalobservationshowedinflammatorycuffaroundsmallbloodvessels,demyelization,degenerationofneurons,andaxonalinjuryinbrainandspinalcordofmiceinEAEgroups.Fociofdiseaseinbrainandspinalcordweres