褪黑素对癫痫状态大鼠海马GAD67 mRNA表达的影响

Effect of melatonin on GAD67 mRNA expression in post-SE rat hippocampus induced by pilocarpine

目的从神经递质角度探讨褪黑素(melatonin,Mel)抗癫痫作用的机制。方法采用匹罗卡品(pilocarpine,PILO)诱发大鼠癫痫持续状态(status epilepticus,SE)模型,观察大鼠SE后4个时相点即6、48、72h和7d海马GABA含量和GAD67mRNA表达的变化,以及Mel对其变化的影响。结果PILO诱导大鼠SE后6h至7d,海马GABA含量显著降低,与对照组比较差异极显著(P<0.01),GAD67mRNA的表达于SE后6～72h较对照组明显降低(P<0.01),SE后7d,GAD67mRNA的表达升高并明显高于对照组(P<0.05);PILO+Mel组大鼠SE后6h至7d,海马GABA水平显著高于PILO组(P<0.01),并且GAD67mRNA的表达在SE后6～72h,也显著高于PILO组大鼠(P<0.05)。结论Mel可能通过上调GAD67mRNA的表达,使GABA合成增加,抑制功能增强来发挥抗癫痫作用。

Objective To probe the mechanism of anticonvulsant by melatonin from the angle of neurotransmitter. Methods Rat status epilepticus （SE） model was induced by pilocarpine（PILO）. γ-aminobutyric acid （GABA） content and glutamin acid decarboxylase （GAD）67 mRNA expression was detected at 6, 48, 72 h, and 7 d in the hippocampus of post-SE rats. The effect of melatonin on these changes was observed. Results GABA content was significantly lower in the hippocampus than in control（ P 〈 0. 01 ）. At 6 -72 h post- SE, the expression of GAD67 mRNA was significantly lower in PILO group than in control（P 〈 0. 01 ） , but significantly higher in PILO group than in control at 7 d post-SE. The content of GABA was significantly higher in PILO ＋ Mel group than in PILO group at 6 h -7 d post-SE（P 〈0. 01 ）and the expression of GAD67 mRNA was significantly higher in PILO ＋ Mel group than in PILO group at 6 - 72 h post-SE （ P 〈 0. 05 ）. Conclusion Anticonvulsive effect of melatonin may be due to its ability to increase the expression of GAD67 mRNA, so to increase the content of GABA.