《中国康复理论与实践》 ›› 2005, Vol. 11 ›› Issue (12): 975-977.

• 专题 • 上一篇    下一篇

LY367385对谷氨酸钠及缺糖缺氧引起的培养小鼠大脑皮层神经元损伤的保护作用

董丽萍; 韩明; 袁芳   

  1. 北京市神经外科研究所 北京市 100050
  • 收稿日期:2005-06-13 出版日期:2005-12-25 发布日期:2005-12-25

The protective effect of LY367385 on impairment of cultured mouse cerebral cortical neurons induced by sodium glutamate or oxygen-glucose deprivation

DONG Li-ping, HAN Ming, YUAN Fang   

  1. Beijing Neurosurgical Institute, Beijing 100050, China
  • Received:2005-06-13 Published:2005-12-25 Online:2005-12-25

摘要: 目的观察LY367385对谷氨酸钠(Glu)及缺糖缺氧(OGD)引起的小鼠大脑皮层神经元损伤的保护作用。方法以细胞乳酸脱氢酶(LDH)漏出、光镜下细胞形态变化为指标,观察培养液中加入Glu或因OGD引起的神经元损伤,以及LY367385的保护作用;用免疫细胞化学和免疫荧光染色法检测神经元代谢型谷氨酸受体1α(mGluR1α)的表达。结果OGD1h或0.1mmol/L的Glu可明显造成神经元损伤,使LDH漏出明显增加(P<0.01);LY367385(50μmol/L)可明显拮抗OGD或Glu引起的神经元损伤,使LDH漏出明显减少(P<0.01);免疫组化检测显示体外培养神经元mGluR1α阳性表达。结论OGD或Glu可能通过激活皮层神经元mGluR1α引起神经元损伤,LY367385通过拮抗mGluR1α保护神经元。

关键词: 神经元, 谷氨酸, 缺糖缺氧, 代谢型谷氨酸受体1α, LY367385

Abstract: ObjectiveTo investigate the protective effect of LY367385 on impairment of cultured mouse cerebral cortical neurons induced by sodium glutamate (Glu) or oxygen-glucose deprivation (OGD).MethodsNeuron damage induced by Glu or OGD, as well as the action of (S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385) were measured by determining the leakage of lactate dehydrogenase (LDH) from neurons. Immunocytochemistry and immunofluorescent methods were used to detect the expression of anti-mGluR1α. Morphological observation of primary cortical neurons was performed by phase contrast microscope.ResultsFollowing the exposure to 0.1 mmol/L Glu for 1 h or OGD for 1 h, LDH leakage from neurons obviously increased (P< 0.01 ). 50 mmol/L LY367385, when co-incubated with Glu or OGD, markedly reduced the LDH leakage (P<0.01). The 24-h leakage of LDH was increased from cells exposed to 0.1 mmol/L Glu for 15 min. Pre-and post-treatment with LY367385 (50 mmol/L ) decreased the leakage of LDH. The cultured neurons expressed mGluR1α.ConclusionLY367385 has protective effect on neurons damaged by Glu or OGD. It may be related to antagonizing mGluR1α.

Key words: neuron, glutamate acid (Glu), oxygen-glucose deprivation, metabotropic glutamate receptors 1α(mGluR1α), LY367385