摘要
目的:建立PM2.5短期暴露自身免疫性疾病动物模型,探讨PM2.5的“暴露时间窗”对小鼠实验性自身免疫性脑脊髓炎(EAE)发生发展的作用机制。方法:完全弗氏佐剂混合MOG35-55免疫6周龄雌性C57BL/6小鼠构建EAE模型。对EAE小鼠进行PM2.5短期暴露,每天观察小鼠临床发病情况。组织学分析结合流式细胞术评估PM2.5短期暴露影响疾病发展的作用机制。结果:EAE小鼠临床评分显示,PM2.5短期暴露可显著延迟疾病发生发展。与对照组相比,PM2.5短期暴露组小鼠中枢神经系统(CNS)中观察到炎症和脱髓鞘显著减少。PM2.5短期暴露小鼠中枢及外周中激活的树突状细胞、巨噬细胞及致病性Th17细胞比例显著降低,有效抑制了CNS及外周炎症。结论:短期暴露于PM2.5环境对EAE小鼠病情具有一定缓解作用,可能通过抑制免疫细胞过度活化、诱导免疫耐受实现,阐明其机制可为自免疫疾病发病机制研究提供依据。
Objective:To establish an animal model of autoimmune diseases with short-term exposure of PM2.5 and to investigate mechanism of"exposure time window"of PM2.5 on development and progression of experimental autoimmune encephalomyelitis(EAE)in mice.Methods:EAE model was constructed by immunizing 6-week-old female C57BL/6 mice with complete Freund's adjuvant mixed with MOG35-55.Clinical pathogenesis of EAE mice was observed everyday under short-term exposure to PM2.5.Mechanism by which short-term PM2.5 exposure affected disease development was assessed by histological analysis combined with flow cytometry.Results:Clinical scores of EAE mice showed that short-term PM2.5 exposure could significantly delay onset and development of EAE.Significantly reduced inflammation and demyelination were observed in central nervous system(CNS)of PM2.5 short-term exposed EAE mice compared to control group.Proportions of activated dendritic cells,macrophages and pathogenic Th17 cells in CNS and periphery of EAE mice short-term exposed to PM2.5 were significantly reduced,effectively inhibiting CNS and peripheral inflammation.Conclusion:Short-term exposure to PM2.5 environment has a certain degree of alleviating effect on condition of EAE mice,which may be achieved by inhibiting immune cell hyperactivation and inducing immune tolerance,providing a basis for elucidation of its mechanism and study of pathogenesis of autoimmune diseases.
作者
韩冰
赵卓华
申玉霞
张言
徐妍
张媛(指导)
HAN Bing;ZHAO Zhuohua;SHEN Yuxia;ZHANG Yan;XU Yan;ZHANG Yuan(College of Life Sciences,Shaanxi Normal University,Xi'an 710119,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2023年第10期2122-2125,2131,共5页
Chinese Journal of Immunology
基金
国家自然科学基金面上项目(82071396)
中央高校基本科研业务费重点项目(GK201802010)
陕西师范大学研究生领航人才培养项目(LHRCYB23003)
陕西省2021年大学生创新创业训练计划项目(S202110718278)。
关键词
实验性自身免疫性脑脊髓炎
细颗粒物
神经炎症
脱髓鞘
免疫耐受
Experimental autoimmune encephalomyelitis
Particulate matter
Neuroinflammation
Demyelination
Immune tolerance