银杏内酯B对谷氨酸诱导海马神经元损伤的影响

EFFECTS OF GINKGOLIDE B AGAINST DAMAGE OF CULTURED HIPPOCAMPAL NEURONS CAUSED BY GLUTAMATE

目的观察银杏内酯B(ginkgolide B,GB)在不同给药模式下对谷氨酸所致海马神经元损伤的影响。方法采用CO2超临界萃取的方法制备GB,建立新生Wistar大鼠原代培养的海马神经元谷氨酸毒性模型,采用台盼蓝染色、程序性细胞死亡检测技术及乳酸脱氢酶测定的方法,观察预处理与急救两种给药模型下不同剂量GB的神经保护作用,并与MK-801急性给药相比较。结果GB在两种给药模式下均能不同程度地提高细胞存活率,降低凋亡率,减少LDH漏出量,且在一定范围内保护作用呈剂量依赖的方式。其中预处理的效果明显优于急救给药处理,但均弱于MK-801组。结论GB对谷氨酸细胞毒性损伤有保护作用,预防性用药效果更佳。GB可能不仅仅通过拮抗血小板活化因子(PAF)受体等下游事件实现其神经保护作用。如果我们重视其预处理给药的显著效果,将其用于高危人群的预防干预可能有更大价值。

To investigate protective effects of ginkgolide B（GB） in different administration modes on glutamate-induced neuronal damage. Methods： Essential GB were obtained by supercritical CO2 fluid extraction. Glutamate excitotoxicity were examined in pri-mary cultures from neonatal Wistar rat, by using of Trypan blue dye staining, testing the lactate dehydrogenase leakage from cultured neurons and terminal deoxynucleotidyl transferase-mediated nick end labeling（TUNEL） method. The protective effects of GB in dif-ferent administration modes（pre-treatment and post-treatment） were adopted and compared with the NMDA receptor uncompetitive antagonist-MK-801 in acute-treatment. Results.Treatment with GB in two administration modes both could increase ratio of surviv-ing neuron, decrease LDH efflux and reduce ratio of neuron apoptosis in different degree, depended on dose in certain range. The pro-tective effect of pre-treatment was superior to post-treatment, but inferior to MK-801. Conlusion： GB can protect neurons against glutamate damage, and preventive using has more efficiency. The potential mechanism of its neural protection may be not only related to PAF receptor. If the predominant protection effect of GB in pretreatment is considered, precautionary intervention to high-risk population could have more value.