C57BL／6小鼠性别差异对髓鞘少突胶质糖蛋白诱导的实验性自身脑脊髓炎疾病的影响  

Gender Influence on The Pathogenesis of EAE Induced by MOG in C57BL/6 Mice

作　　者：王婷婷[1] 杜昌升[1] 

机构地区：[1]上海市信号转导与疾病研究重点实验室、同济大学生命科学与技术学院受体生物医药实验室,上海200092

出　　处：《生物化学与生物物理进展》2013年第11期1116-1123,共8页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(31000399,31171348);国家重点基础研究发展计划(973)(2012CB910404)资助项目~~

摘　　要：多发性硬化是人类常见的中枢神经系统自身免疫性炎症致脱髓鞘疾病.流行病学研究发现,女性患者多于男性,其平均发病时间早于男性.实验性自身免疫性脑脊髓炎(EAE)与多发性硬化症有相似的临床症状和病理特征,是被广泛应用于人类疾病研究的动物模型.本实验利用髓鞘少突胶质糖蛋白MOG33-35免疫C57BL/6小鼠建立EAE模型,观察29天.通过疾病评分发现雌雄小鼠在发病率、起病时间上均无明显差别,但雄鼠的发病症状明显比雌鼠严重.在其病理切片HE染色中观察到雄性小鼠中枢浸润的炎性细胞多于雌性小鼠,并且在LFB染色中同样观察到雄鼠脱髓鞘区域明显增大.对其发病高峰期中枢浸润细胞的染色分析时,可以发现雄性小鼠中浸润的CD4+T细胞及其亚群T H-1和T H-17细胞均有明显增加.这些都表明MOG33-35免疫C57BL/6小鼠建立的EAE模型存在着性别差异的影响,这一发现为今后建立多发性硬化症的动物模型中动物性别的选择提供了一定的参考依据.Multiple sclerosis （MS）, an autoimmune disease of the CNS with prominent demyelination and axonal degeneration, is more prevalent in women than men. EAE is a widely used animal model of MS for preclinical therapy development. In this report, a 29 days observation of the EAE model induced by MOG33-35 in C57BL/6 mice was performed. From the clinical course, we found no significant difference between male and female mice in the incidence and onset time, but males had a more serious disease score than that in females. And histological examination of spinal cord was performed at day 21 post-immunization. Compared with male mice, female mice had a dramatic increase of leukocyte infiltration in the spinal cord. Luxol fast blue staining also revealed enhanced demyelination in male mice compared to female mice. The CNS leukocyte infiltration was also quantified by flow cytometry analysis at day 19 post-immunization. The results again confirmed that the CD4＋ T cells accumulated in the CNS of EAE mice were increased in male mice. We further quantified the number of TH-l and TH-l7 cells in the CNS infiltrates and found that the absolute number of both TH-17 and Tn-1 cells were significantly increased in male mice. Taken together, these data indicate that sex difference exists in EAE induced by MOG33.35 in C57BL/6 mice, and this will provided useful indications for further studies on the selection of animals in the EAE model.

关 键 词：C57BL/6小鼠 实验性自身脑脊髓炎 性别差异 

分 类 号：R392.1[医药卫生—免疫学]