基础医学与临床 ›› 2007, Vol. 27 ›› Issue (10): 1109-1112.

• 研究论文 • 上一篇    下一篇

NMDAR1单克隆抗体抑制谷氨酸诱导的大鼠海马神经元Ca2+内流

吴兰香 孙长凯 范明 丁爱石   

  1. 大连医科大学脑疾病研究所
  • 收稿日期:2006-09-29 修回日期:2006-11-29 出版日期:2007-10-25 发布日期:2007-10-25
  • 通讯作者: 吴兰香

Anti-NR1 monoclonal antibody attenuates the glutamate-induced intracellular free calcium increase in rat hippocampal neurons

  

  • Received:2006-09-29 Revised:2006-11-29 Online:2007-10-25 Published:2007-10-25

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。

Abstract: Objective To study the effect of mAbN1, a monoclonal antibody against N-methyl-D-aspartate receptor subunit 1 (NR1) on Ca2+ influx after glutamate stimulation in rat cultured hippocampal 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 ([Ca2+]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 compared with MK-801, mAbN1 can more significantly attenuate the glutamate-induced [Ca2+]i increase, and it has no effect on [Ca2+]i in physiological condition. Conclusion mAbN1 maybe alter the secondary structure of NR, consequently influence Ca2+ influx in excitotoxicity process