摘要
目的:制作不同基因背景小鼠自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)模型,比较不同遗传背景小鼠发病、神经功能评分和病理变化的差异。方法:用髓鞘少突胶质细胞糖蛋白抗原(MOG35-55)免疫C57BL/6和CD-1基因背景小鼠,用完全弗氏佐剂作为抗原载体,并在不同时间点用精制百日咳毒素增强免疫效果,建立自身免疫性脑脊髓炎模型;记录小鼠发病时间与表现,每天进行神经功能评分,并取其脑和脊髓组织进行病理学检查和以CD4、IL-17为靶标的免疫组化染色。结果:C57BL/6组小鼠发病高峰期出现于初次免疫后17～25 d,表现典型的拖尾、单侧或双侧后肢瘫痪等改变,神经功能评分在3分左右;CD-1组小鼠发病高峰期较C57BL/6组推迟,出现于免疫后35～40 d,可见相似的拖尾及偏瘫表现,神经功能评分在2.8分左右。病理检查可见C57BL/6模型小鼠脑、脊髓出现炎症性细胞浸润,而CD-1小鼠的炎性改变相对较轻、且主要出现于脊髓;罗克沙尔固蓝染色法鉴定显示,模型小鼠脑脊髓组织出现脱髓鞘病变,以C57BL/6小鼠更为严重。免疫组织化学法显示2种模型小鼠发病高峰期均存在不同程度的CD4+及IL-17+炎性细胞的浸润。结论:不同的遗传背景对EAE模型发病、临床表现和病理改变有明显影响;CD-1小鼠亦可运用于制作慢性迁延性EAE模型,更符合人类多发性硬化的特点。
Objective：In order to establish different mouse models of experimental autoimmune encephalomyelitis（EAE）,compare the features of development,clinical scores and pathological analysis in different gene background.Methods：Mice were induced by myelin oligodendrocyte glycoprotein（MOG35-55） peptide in complete Freund＇s adjuvant（CFA）,also received pertussis toxin twice for immune enhancement,established EAE mice models with record the onset time,clinical manifestation,nerves function scores for daily.Finally the spinal cord and brain tissues were taken for pathological analysis with CD4 and IL-7 immunocytochemistry staining.Results：C57BL/6 mice reached the peak of clinical scores at 17 to 25 days after first induction,and showed typical performance like limp tail and partial or complete limb paralysis.The mean clinical score was 3.0.CD-1 mice put off the peak till 35 to 40 days after first induction compared with C57BL/6 mice.CD-1 mice also showed limp tail or limb paralysis with similar performance.The mean clinical score was 2.8.The results of H.E.and Luxor fast blue analysis showed CD-1 mice changing were lighter than C57BL/6 mice,most manifestations occurred in spinal cord.While immunochemistry analysis results showed CD4＋ and IL-17＋ lymphocytes infiltration in varying degrees.Conclusion：Different gene background have apparently influence on susceptibility,clinical performance and pathological changing in EAE model.CD-1 mice can also be used to produce chronic EAE model,with the characteristics coincide with multiple sclerosis.
出处
《南京医科大学学报（自然科学版）》
CAS
CSCD
北大核心
2013年第6期771-778,共8页
Journal of Nanjing Medical University(Natural Sciences)
基金
南京医科大学科技发展基金重点项目(2010NJMUZ32)
