中山大学学报(医学科学版)2018,Vol.39Issue(2):207-214,244,9.
小鼠脑实质注射水通道蛋白4抗体所致的病理损伤
Lesions Caused by Intracerebral Injection of Aquaporin-4 Immunoglobulin G
摘要
Abstract
[Objective]To investigate the pathological damage caused by aquaporin-4 antibody extracted from patients with neuromyelitis optica spectrum disorders(NMOSD)and the influence of systemic immune status on the local disease focus.[Methods]The C57BL/6 mice were chose for establishing experimental autoimmune encephalomyelitis (EAE).During the peak at onset,serum-derived immunoglobulin G(IgG)from aquaporin-4(AQP4)IgG positive patients and healthy human complement(hC)were injected in the brain parenchyma(EAE+AQP4-IgG+hC group,n=5).The EAE induced mice injected with normal saline(EAE+NS group,n=5)and mice without EAE injected with AQP4-IgG and hC from healthy volunteers(AQP4-IgG + hC group,n=5)were served as control groups. The dramatic loss of AQP4,astrocyte glial fibrillary acidic protein(GFAP),oligodendrocyte myelin basic protein(MBP)and the infiltration of inflammatory cells(T lymphocytes,neutrophils and macrophages)were compared with each group by using immunoflu-orescence,in order to find abnormal changes.[Results]Intracerebral injection of AQP4-IgG together with hC can cause NMO-like lesions,including astrocyte injury,demyelination and inflammatory cell infiltration.However,EAE mice model with intracerebral injection of AQP4-IgG and hC represented more significant loss of AQP4 and GFAP(P=0.008 and P=0.016,respectively)compared with mice without EAE induced.The area of MBP loss was also increased,while there′s no statistical difference.No statistical difference was also found in the number of vessels infiltrated with CD3+T cell,neu-trophils and the area infiltrated with macrophage. Astrocyte proliferation existed in all groups,but no loss of AQP4, GFAP and MBP was found in EAE mice injected with NS.[Conclusion]Intracerebral injection of AQP4-IgG and hC can cause distinct pathological damage and the pathology can be promoted by immune system activated by EAE.Intracerebral injection of AQP4-IgG and hC can mimic the pathogenesis of NMOSD better in EAE mice model.关键词
视神经脊髓炎谱系疾病/水通道蛋白4抗体/动物模型/实验性自身免疫性脑脊髓炎Key words
neuromyelitis optica spectrum disorders/aquaporin-4 immunoglobulin g/animal models/experimental autoimmune encephalomyelitis分类
医药卫生引用本文复制引用
方羚,陈晨,康新梅,孙晓渤,周一凡,黄巧,彭立胜,邱伟..小鼠脑实质注射水通道蛋白4抗体所致的病理损伤[J].中山大学学报(医学科学版),2018,39(2):207-214,244,9.基金项目
国家自然科学基金(8177050896) (8177050896)
广东省自然科学基金(2017A030313853) (2017A030313853)