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粉防已碱对体外培养大鼠脑皮层神经元损伤的保护作用

车建途, 张均田, 陈飞松, 屈志炜   

  1. 1. 中国医学科学院, 协和医科大学药物研究所药理二室, 北京 100050;
    2. 北京中医研究所药理实验室, 北京 100010
  • 收稿日期:1996-06-02 修回日期:1997-03-09 出版日期:1997-09-15 发布日期:1997-09-15

Protective Effect of Tetrandrine against Excitatory Amino Acids induced Neuronal Injury in Cortical Culture

Jian-Tu Che, Jun-Tian Zhang, Fei-Song Chen, Zhi-Wei Qu   

  1. 1. Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050;
    2. Pharmacological Laboratory, Beijing Institute of Traditional Chinese Medicine, Beijing 100010
  • Received:1996-06-02 Revised:1997-03-09 Online:1997-09-15 Published:1997-09-15

摘要: 兴奋性氨基酸类神经毒剂与粉防己碱(tetrandrine, Tet)共同作用于原代培养胎鼠大脑皮层神经元24小时, 发现10-7, 10-6 mol·L-1 Tet明显降低50 μmol·L-1谷氨酸(glutamate, Glu), 300 μmol·L-1 β-N-methylamino-L-alanine (BMAA, NMDA受体激动剂)20 μmol·L-1 β-N-oxalylamino-L-alanine (BOAA, non-NMDA受体激动剂)导致的培养液乳酸脱氢酶(lactate dehydrogenase, LDH)活性的增高; 细胞形态损害减轻, 细胞数量增加。对20 μmol·L-1 NMDA介导的神经元损伤改变无影响。提示Tet对某些Glu类神经毒剂引起的胎鼠大脑皮层神经元损伤有一定保护作用, 其机制可能是抑制细胞膜上的Na+通道开放, 阻止膜去极化而影响电压依赖性Ca2+通道启动。对NMDA受体可能亦有一定作用。

关键词: 粉防己碱, 大脑皮层神经元, 兴奋性氨基酸

Abstract: The ability of tetrandrine (Tet), an alkaloid isolated from Radix Stephaniae Tetrandrae, to reduce cortical neuronal injury in cortical cultures derived from fetal rats was quantitatively assessed by examination of morphological changes and measurement of lactate dehydrogenase (LDH) released to the extracellular bathing media. Cell cultures exposed to the excitatory amino acids (EAA)-50 μmol·L-1 glutamate (Glu), 20 μmol·L-1 N-methyl-D-aspartate (NMDA), 300 μmol·L-1 β-N-oxalylamino-L-alanine (BMAA, NMDA receptor agonist) or 20 μmol·L-1 β-N-oxaly-lamino-L-alanine (BOAA, non-NMDA receptor agonist)for 24 h at 37 ºC showed widespread neuronal injury. Tet had little effect on the injury induced by 20 μmol·L-1 NMDA but 10-7 and 10-6 μmol·L-1 Tet did partially attenuate the neuronal degeneration, neuronal loss and LDH efflux resulting from prolonged exposures to 100 μmol·L-1 Glu, 300 μmol·L-1 BMAA and 20 μmol·L-1 BOAA respectively. The ability of Tet to reduce the neuronal injury induced by prolonged exposure to EAA may contribute, at least in part, to the reduction of Ca2+ influx through inhibiting the opening of voltagegated Ca2+ channels. Another mechanism that Tet might have a little inhibitory effect on NMDA receptor on neuronal membrane cannot be excluded, as BMAA has been considered to act as a weak NMDA receptor agonist.

Key words: Tetrandrine, Cortical neuronal culture, Intracellular Ca2+, Excitatory amino acids

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