托吡酯对青霉素诱发大鼠痫性放电和海马区相关递质含量的影响

The effects of topiramate on the epileptiform discharge and related neurotrans mitters in hippocampus in seizure rats induced by penicillin

目的 观察托吡酯对大鼠皮层定位注射青霉素诱发惊厥模型的对抗作用,并探讨其作用机制。方法 建立大鼠皮层定位注射青霉素诱发惊厥模型,观察两种剂量托吡酯ig给药对青霉素诱发痫性发作的程度和海马区痫性放电的潜伏期、痫波发放频率及痫波最高波幅的影响;采用HPLC法测定惊厥大鼠海马区Glu、Asp、Gly、GABA含量的变化。结果 两种剂量托吡酯(110, 440mg·kg-1,ig)均可减轻大鼠惊厥发作的程度,延长痫性放电的潜伏期,减少痫波发放频率,减小放电最高波幅,与模型组比较,差异均具有显著性(P<0 05或P<0 01)。同时,均可使大鼠海马区Glu含量降低,GABA含量升高,与模型组比较差异均有显著性 (P<0 05或P<0 01)。结论 托吡酯可明显抑制皮层定位注射青霉素诱发的痫性发作和痫性放电, 产生抗惊厥作用。其作用机制可能与加强GABA抑制功能和限制Glu兴奋功能有关。

Aim To investigate the effects of topiramate (TPM) o n the model of seizure rats induced by penicillin and explore its mechanism of ant iconvulsant action.Methods Using the model of seizure rats indu ced by penicillin localized injected in cortex, we investigated the effect of TP M on the changes of seizure extent and recorded the latency of epileptiform disc harge, frequency of epileptiform wave, highest wave of hippocampus EEG. The leve ls of Glu, Asp, Gly and GABA in hippocampus were determined by high performance liquid chromatography (HPLC). Results Compared with the model g roup, TPM (110 mg·kg -1, 440 mg·kg -1, ig) could significantly light ened the extent of seizure, prolonged the latency of epileptiform discharge, red uced the frequency of epileptiform wave and minished the highest wave of hippoca mpus EEG (P<0.05 or P<0.01). Moreover, the level of Glu decreased and that of GABA increased in the two groups of TPM (P<0.05 or P<0.01). Conclusion TPM can significantly inhibit the seizure extent and ep ileptiform discharge in seizure rats induced by penicillin localized injected in cortexl and induce anticonvulsant action. Its mechanism of anticonvulsant actio n might due to decrease in Glu level and increase in GABA level.