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作 者:廖玉芳[1] 王华坤[1] 肖奕[1] 张艳欣[1] 王新风[1] 王明正[1]
出 处:《中国药学杂志》2012年第2期108-112,共5页Chinese Pharmaceutical Journal
基 金:山西医科大学创新基金资助课题(01200804)
摘 要:目的研究4-氨基-2-甲基斑蝥胺(AMC)的抗惊厥作用及对皮层脑电图(EcoG)、γ-氨基丁酸(GABA)和γ-氨基丁酸受体(GABAB)受体的影响。方法建立大鼠皮层运动区定位注射青霉素诱发惊厥(PIC)模型,以丙戊酸钠(VPA)为阳性对照,以惊厥潜伏期和Racine分级评定药效,RM6240C型多道生物信号采集处理系统同步记录惊厥大鼠EcoG,分析灌胃AMC(25.0,100.0 mg.kg-1)后的抗惊厥作用及对EcoG影响。采用免疫组化技术,测定皮层和海马区GABA和GABAB受体蛋白量的变化。结果两剂量AMC均能显著减轻大鼠惊厥发作及癫痫样脑电(P<0.01);小剂量AMC组皮层和海马GABA含量虽然均较正常组和模型组高,但差异无显著性(P>0.05);海马部位的GABAB受体蛋白表达量升高(P<0.05),而在皮层部位的表达量虽然较模型组高,但差异无显著性(P>0.05)。VPA组和大剂量AMC组皮层、海马区GABA含量与GABAB受体蛋白表达量均显著升高(P<0.05)。结论 AMC可对抗PIC惊厥,抑制痫性放电。抗惊厥作用的机制与提高皮层和海马区的GABA含量和GABAB受体表达有关。OBJECTIVE To investigate the anticonvulsion effect of 4-amino-2-methyl cantharidinmide (AMC) and its influences on epileptiform electroencephalogram (EcoG), contents of γ-aminobutyric acid (GABA)and GABAR receptor. METHODS Rat model of penicillin-induced-convulsi0n(PIC) was established by intracortical (ic) penicillin (PNC) injection in rat motor cortex. Valproate (VPA) was used as the positive control drug. Convulsion seizure latency and racine behavior study graduations were used as in- dexes to evaluate the efficacy. RM6240C multi-channel biological signal collection-processing system synchronously recorded EcoG of convulsive rats 'after intragastfic (ig) administration of AMC (25.0,100. 0 mg ·kg^-1 ). The effects on convulsion and epileptiform dis- charge were analyzed. The contents of GABA and the expression of GABAB receptor in the cortex and hippocampus regions of rats were determined by immunohistochemistry technique. RESULTS AMC at the two doses and VPA could reduce epileptiform activities and discharge and prolong the latencies of epilepsy seizure, compared with the PIC group (P 〈 0. 01 ). In the rats treated with AMC at 10w dosage, the GABA contents in cortical and hippocampal regions were higher than those in normal control and model groups, but with no statistes .significance (P 〉 0. 05 ) ; compared with model control, the expression quantity of hippocampal GABAB receptor protein was significantly increased (P 〈 0. 05), while the increase in cortex was not significantlY different (P 〉 0. 05 ). GABA expression quantity in groups Of larger dosage AMC and VPA were respectively higher than that in the normal group and the model group, and the GABAB receptor protein expression quantity also significantly increased ( P 〈 0. 05 ). CONCLUSION AMC can antagonize the convulsion seizure and inhibit the epileptiform discharge induced by penicillin in rats. The anti-convulsion mechanism of AMC is possibly related with increasing GABA'content
关 键 词:4-氨基-2-甲基斑蝥胺 抗惊厥作用 Γ-氨基丁酸 Γ-氨基丁酸受体
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