NMDAR1单克隆抗体抑制谷氨酸诱导的大鼠海马神经元Ca^(2+)内流  

Anti-NR_1 monoclonal antibody inhibits the glutamate-induced intracellular free calcium increase in rat hippocampal neurons

作　　者：吴兰香[1] 孙长凯[1] 范明[2] 丁爱石[2] 

机构地区：[1]大连医科大学脑疾病研究所,辽宁大连116027 [2]军事医学科学院基础医学研究所,北京100850

出　　处：《基础医学与临床》2007年第10期1109-1112,共4页Basic and Clinical Medicine

基　　金：国家自然科学基金(30070267);中国博士后科学基金(2001);辽宁省重点科技攻关课题(2001226005)

摘　　要：目的观察人N-甲基-D-门冬氨酸受体(NMDAR,NR)主亚基(NR1)单克隆抗体mAbN1对谷氨酸诱导的大鼠海马神经元Ca2+内流的影响。方法建立谷氨酸介导的大鼠海马神经元兴奋毒性损伤模型,以mAbN1及MK-801分别预处理海马神经元,用Fluo-3/AM法,在激光扫描共聚焦显微镜下观察对细胞内游离Ca2+浓度([Ca2+]i)的影响。结果mAbN1能显著抑制谷氨酸所致海马神经元[Ca2+]i升高,此作用强于MK-801,且其本身对生理状态下神经元[Ca2+]i无影响。结论mAbN1的抗兴奋毒性作用可能是通过改变NR的蛋白质二级结构从而影响兴奋毒性作用中的Ca2+内流实现的。Objective To study the effect of mAbN1 , a monoclonal antibody subunit 1 （NR1） on Ca^2＋ influx after glutamate stimulation in cultured rat hi against N-methyl-D-aspartate receptor ppocampal neurons. Methods Excitotoxicity was induced by glutamate in cultured hippocampal neurons. Confocal laser scanning microscopy was used to observe the changes in intracellular free calcium concentration （ [ Ca^2＋ ] i ） at the level of cultured hippocampal neurons following pretreatment with mAbN1 and MK-801. Intracellular free calcium was imaged after loading cells with the fluorescent dye indicator fluo-3/AM. Results Our findings indicate that as compared with MK-801, mAbN1 can more significantly attenuate the glutamate-induced [ Ca^2＋ ]i increase, and it has no effect on [ Ca^2＋ ] i in physiological condition. Conclusion mAbN1 may alter the secondary structure of NR, consequently influence Ca2 ~ influx in excitotoxicity process.

关 键 词：兴奋毒性 神经保护 海马神经元 单克隆抗体 共聚焦显微镜 

分 类 号：R392[医药卫生—免疫学]