石菖蒲α-细辛醚对Lithium-Pilocarpine癫痫模型GABA系统的调控作用

Effect of alpha-asarone on regulation of GABA system in the Lithium-Pilocarpine model of epilepsy

目的探讨石菖蒲α-细辛醚治疗对Lithium-Pilocar-pine模型大鼠抗癫痫作用可能的分子机制。方法建立Lithium-Pilocarpine模型,通过观察α-细辛醚治疗对Lithium-Pilocarpine模型大鼠GABA含量、GAD67表达、GABA-T活性及GABAA受体表达的影响。结果①模型组大鼠癫痫持续状态(Status epilepticus,SE)后12 h～24 h海马GABA含量及GAD67表达明显降低(P<0.01),持续至SE后72 h,之后缓慢增高;②SE后各时相脑内GABA-T活性明显增高(P<0.01),以海马区GABA-T活性增高最为突出,持续至SE后1周仍明显高于正常对照组;③SE后12 h～24 h脑内GABAAR-mRNA表达明显降低,GABAAR-mRNA表达高峰主要发生在SE后48 h～72 h;④石菖蒲α-细辛醚治疗能显著增加大鼠SE后各时相海马GABA含量,增强GAD67及GABAA-RNA表达,并持续数日以上,至SE后1周恢复正常;能降低SE后增高的GABA-T活性,其下调海马区GA-BA-T活性的作用强于额叶。结论石菖蒲α-细辛醚可能通过抑制GABA-T活性以降低GABA分解代谢,上调GAD67表达使GABA合成增加,上调GABAA受体表达以增强GA-BA介导的抑制功能来发挥抗癫痫作用。

Aim To investigate the molecular mechanism of antiepileptic effect of alpha-asarone on Lithium-Pilocarpine model.Methods Rat status epilepticus（SE） model was induced by Lithium-Pilocarpine.Rats were sacrificed at the 12 h,24 h,48 h,72 h and 1 week after SE to dynamically observe GABA content,GAD67 expression,GABA transaminase（GABA-T） activity and expression of GABAA receptor.The effect of alpha-asarone on these changes was observed.Results GABA content and GAD67 expression in the hippocampus were markedly decreased at 12 h^24 h（P0.01） and increased gradually after 72 h.The GABA-T activities in the frontal lobes,especially the hippocampus,were significantly increased at different time point（P0.05） and still higher than those in normal control group at one week post-SE.At12 h^24 h after SE,the expression of GABAAR-mRNA were significantly lower in Lithium-Pilocarpine model group than in normal control group（P0.01）.The expression of GABAAR-mRNA were markedly increased and reached to maximum level at 48 h～72 h post-SE.The content of GABA and the expression of GAD67 and GABAAR-mRNA were significantly higher in alpha-asarone treated group than in Lithium-Pilocarpine model group at 12h～7d post-SE（P0.05）.The activity of GABA-T in the frontal lobes and the hippocampus were significantly lower in alpha-asarone treated group than in Lithium-Pilocarpine model group at different time point（P0.05）.Conclusions The antiepileptic effect of alpha-asarone seems to be directly related to its role in upregulating GABA content and the expression of GAD67 and GABAAR mRNA,and down regulating GABA-T activity.