蝇蕈醇激动GABA_C受体对青霉素致大鼠癫痫的影响  

Effects of GABA_C receptor activation with muscimol on penicillin-induced epileptic seizures in rats

作　　者：范彦英[1] 廖玉芳[1] 肖奕[1] 张艳欣[1] 王明正[1] 

机构地区：[1]山西医科大学基础医学院药理教研室,太原030001

出　　处：《山西医科大学学报》2014年第4期267-271,共5页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(81202520);山西医科大学创新基金资助项目(01200804)

摘　　要：目的研究激动GABAC受体对青霉素诱导的大鼠癫痫发作、痫性放电的影响,探讨激动GABAC受体在内源性抗癫痫机制中的作用。方法青霉素致痫大鼠模型采用皮层定位注射青霉素(200 U)法制作。将144只成年健康SD大鼠随机分成四组:正常对照组,癫痫模型组,荷包牡丹碱(GABAA受体阻断剂)+高牛磺酸(GABAB受体阻断剂)处理组,和荷包牡丹碱+高牛磺酸+蝇蕈醇(GABAC受体激动剂)处理组。以癫痫发作持续时间和Racine痫性行为学分级作为效应指标;同步记录癫痫大鼠皮层脑电图(EcoG),分析痫样波持续时间、发放频率及最高振幅。结果大鼠运动皮层定位注射青霉素后,均出现Ⅰ-Ⅲ级发作,EcoG出现明显的棘波和棘慢波。癫痫发作高峰期给予荷包牡丹碱和高牛磺酸,可协同青霉素延长发作持续时间,增加发作级别,并增加痫样放电持续时间、频率和痫波振幅(P<0.05)。利用蝇蕈醇激动GABAC受体能明显降低大鼠癫痫发作持续时间、发作级别和痫样放电持续时间(P<0.05 vs荷包牡丹碱+高牛磺酸处理组),并且与癫痫模型组及荷包牡丹碱+高牛磺酸处理组比较,均能显著降低相同时间内的痫样波发放频率和振幅(P<0.05)。结论蝇蕈醇激动GABAC受体可加速终止青霉素与GABAA和GABAB受体阻断剂协同诱发大鼠癫痫发作,抑制痫性放电,提示GABAC受体的激活是内源性的抗癫痫机制之一。Objective To investigate the influence of activating GABAc receptor on penicillin-induced seizures and epileptic dis- charge, and to explore the roles of GABAc receptor activation in the endogenous antiepileptic mechanisms. Methods The epilepsy model was established by intracortical injection of penicillin （200 U）. One hundred and forty-four adult Sprague-Dawley rats were ran- domly divided into fours groups：normal saline group, epilepsy model group, bicuculline （GABAA receptor antagonist） ＋ homotaurine （ GABAB receptor antagonist） group and bicuculline ＋ homotaurine ＋ muscimol （ GABAc receptor agonist） group. The efficacy indi- ces were evaluated according to the seizure duration and Racine＇ s score. Electrocorticography （EcoG） signals of each rat were recorded simultaneously via RM6240C-type multi-channel biological signal acquisition and processing system to analyze the duration, frequency, and maximum amplitude of epileptic discharge. Results After injecting penicillin, the seizure was induced successfully, presented as stage I -Ⅲ of seizures and the epileptiform EcoG activity in all rats. The duration and stage of seizures and the duration, frequency and maximum amplitude of epileptic discharge were increased after injection of bicuculline and homotaurine at the peak period of sei- zures （P 〈 0.05）. Compared with bicuculline ＋ homotaurine group, the seizure duration and stage and duration of epileptic discharge decreased in bicuculline ＋ homotaurine ＋ muscimol group （P 〈 0.05）. In addition, muscimol decreased the frequency and amplitude of epileptic discharge （ P 〈 0.05 versus epilepsy model group ;P 〈 0.05 versus bicuculline ＋ homotaurine group）. Conclusion Acti- vating GABAc receptor by muscimol could accelerate the termination of the seizure and epileptic discharges co - induced by penicillin and GABAA and GABAB receptor antagonists, which imply that GABAc receptor activation is involved in the endogenous antiepileptic mechanisms.

关 键 词：蝇蕈醇 GABAC受体 抗癫痫作用 

分 类 号：R742.1[医药卫生—神经病学与精神病学]