组胺对N-甲基-D-天门冬氨酸诱发的神经元损伤的改善作用

Reversing effect of histamine on neuron death induced by N-methyl-D-aspartate

目的 :在细胞水平探讨组胺对 N-甲基 - D-天门冬氨酸 ( NMDA)诱发的神经元损伤的改善作用及初步机制。方法 :采用原代新生大鼠皮层培养的方法 ,以形态学和二苯基四氮唑溴盐染色为指标观察神经元的损伤和药物的改善作用。结果 :组胺在 10 -4、10 -6、10 -7、10 -8mol/ L浓度时能显著改善 NMDA5 0 μmol/ L作用 3h引起的神经元死亡 ,并在 10 -4和 10 -7mol/ L浓度时分别呈现保护双峰。组胺 10 -7mol/ L的改善作用只被组胺 H2 受体西米替丁逆转 ,而组胺 10 -4mol/ L的改善作用只被 H1受体吡拉明逆转。结论 :组胺能减弱 NMDA诱发的神经元兴奋性死亡 ,其保护作用在低浓度时可能与 H2 受体有关 ,在高浓度时可能与 H1受体有关。

Objective: To determine the effect of histamine on N methyl D aspartate (NMDA) induced neuron death and to elucidate its mechanism. Methods: The primary cortical cell culture was adopted. Neuron morphology and MTT assay were used to evaluate the drugs effects. Results: Histamine at doses of 10 -4 、10 -6 、10 -7 、10 -8 mol/L reversed the neuron death induced by NMDA (50 μmol/L) for 3 h. The protection of histamine peaked at doses of 10 -4 mol/L and 10 -7 mol/L. The effect of histamine of 10 -7 mol/L was reversed only by cimetidine,an H 2 receptor antagonist. However, the effect of histamine of 10 -4 mol/L was reversed only by pyrilamine but not cimetidine. Conclusion: Histamine could reduce neuron death induced by NMDA; its protection at a low dose might be mediated by H 2 receptor, and at a high dose by H 1 receptor.