NMO-IgG对谷氨酸及其受体NMDAR1与NMDAR2B表达的影响

EFFECTS OF NMO-IgG ON THE EXPRESSION OF GLUTAMATE,NMDAR1 and NMDAR2B IN SPINAL CORD OF MICE

目的:研究视神经脊髓炎(NMO)小鼠脊髓体外模型中谷氨酸(Glu)浓度及N-甲基-D-天冬氨酸受体(NMDAR,NR)NR1及NR2B亚单位表达量是否发生改变,探讨NMDA受体介导的Glu兴奋毒性作用参与NMO致病机制的可能性。方法:1提取NMO患者血浆中水通道蛋白4(AQP4)自身抗体(NMO-IgG);2用提纯后的NMO-IgG干预C57BL/6乳鼠脊髓片(脊髓薄片300μm),培养制成NMO组,通过检测胶质纤维酸性蛋白(GFAP)、AQP4评估NMO模型建立是否成功,并进行缺损评分,同时设置不加NMO-IgG和补体的对照组。3比色法检测各组培养液Glu浓度,用免疫组织荧光检测脊髓NR1及NR2B亚单位表达。结果:1NR1、NR2B在NMO组表达量显著高于对照组(P<0.05);2NMO组与对照组Glu浓度比较差异无统计学意义(P>0.05)。结论:NMO-IgG促进小鼠脊髓NMDAR亚单位NR1、NR2B表达;NMDAR可能参与NMO致病。

Objective：To investigate the concentration of glutamic acid（Glu）and the expression of N-methyl-D-aspartate receptor 1（NMDAR,NR1）and NR2 B subunit of NR in spinal cord of neuromyelitis optica（NMO）mice model in vitro,and to explore the possible involvement of NR-mediated Glu excitotoxicity in the pathogenesis of NMO.Methods：①Extraction on autoantibody to aquaporin 4（AQP4,NMO-IgG）from NMO patients;②In NMO group,culturing spinal cord slices（300μm）were treated with purified NMO-IgG;the NMO model was evaluated by the measurements of Glial Fibrillary Acidic Protein（GFAP）and AQP4.③Colorimetric method and Immunohistochemistry were used respectively to detect Glu concentrations in the culture solution and NR1,NR2 Bsubunit expression.Results：The expression of NR1 and NR2B were significantly increased in the NMO-IgG group（P〈0.05）.There was no significant difference in Glu concentration between the NMO group and the control group（P〉0.05）.Conclusion：NMO-IgG promotes the expression of NR1 and NR2Bin spinal cord of mice,NR may be involved in the pathogenesis of NMO.