代谢型谷氨酸受体亚型5拮抗剂MPEP在小鼠癫痫治疗中的作用

Anti-epilepsy activity of a mGluR5 selective antagonist, 2-methyl-6-（phenylethynyl）-pyriding in Swiss mice

目的：观察2-甲基6-苯基乙炔基嘧啶（MPEP）在毛果芸香碱诱导的癫痫小鼠动物模型中的抗抽搐及对小鼠大脑神经元的保护作用。方法：取5—6周瑞士雄性小鼠行颈静脉插管。插管后第3天腹腔注射毛果芸香碱诱导小鼠癫痫模型。待癫痫发作1或2h通过颈静脉插管给予四种不同剂量（25mg／kg，50mg／kg，100mg／kg，200mg／kg）的MPEP（实验组）或10％蓖麻油-生理盐水（实验对照组），观察其抗癫痫活性。给药后24h断头取脑行病理观察，并计算海马齿状回门区中间神经元的密度。结果：与实验对照组相比①25mg／kg，50mg／kg两种剂量组在癫痫发作后1及2h给药均无明显抗抽搐活性，对海马齿状回门区中间神经元亦无明显保护作用（P〉0．05）。②100mg／kg剂量组在癫痫发作后1h及2h给药均有明显抗抽搐活性。1h给药对海马齿状回门区中间神经元密度似有增加，但差异无显著性意义（P〉0．05）；2h给药对海马齿状回门区中间神经元无明显保护作用。③200mg／kg剂量组有更好的抗抽搐活性。1h给药海马齿状回门区中间神经元的密度显著增加（P〈0．05）。2h给药对海马齿状回门区中间神经元无明显保护作用（P〉0．05）。结论：MPEP对毛果芸香碱诱导的癫痫小鼠模型有明显的抗抽搐活性，如果给药及时MPEP对海马齿状回门区中间神经元有明显保护作用，并在实验剂量范围内随着剂量的增加有明显的增强趋势。

Objective：To evaluate the anti-seizure and neuroprotective effect of mGluR5 antagonist, 2-methyl-6- （phenylethynyl）-pyriding （MPEP）, after pilocarpine-induced status epilepticus in swiss mice.Method：Male Swiss mice, about five to six weeks,were used.Cannulation was done through the jugular vein in anaesthetized mouse.After three days of cannulation,the mice were induced with pilocarpine.MPEP was injected through the polythene tubing in the different dosages （25mg/kg,50mg/kg,100mg/kg,200mg/kg） at 1 or 2 hours during status epilepticus.The behavioral change was observed.After 24 hours of injection of MPEP, the mice were killed.The number of neurons in the hilus of dentate gyrus in the dosal hippocampus was counted. Result： ①MPEP at 25mg/kg or 50mg/kg could not stop seizures and neuronal death in the hilus of the dentate gyrus at 1 or 2 hours during pilocarpine-induced status epilepticus. ②MPEP at 100mg/kg could exhibits anti-seizure action,but could not stop the neuronal death in the hilus of the dentate gyrus at 1 or 2 hours during pilocarpine-induced status epilepticus.③MPEP at 200mg/kg had better anti-seizure action than at 100mg/kg at 1 or 2 hours during pilocarpine induced status epilepticus. Simultaneously MPEP at 200mg/kg exhibited the neuroprotective effect （P〈0.05） in the hilus of the dentate gyrus at 1 hours during pilocarpine-induced status epilepticus, but not at 2 hours.Conclusion：MPEP is effective in the prevention of seizures or neuronal death in the epilepsy model of pilocarpine-induced Swiss mice through intravenous injection.