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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 anticonvulsant effect of 4-amino-2-methyl-cantharidin (AMC) and its effect on cortical EEG, GABA and GABAB receptor Impact. Methods The model of penicillin-induced convulsion (PIC) was established by injection of penicillin-induced convulsion in the motor cortex of rats. VPA was used as a positive control. The convulsive incubation period and Racine grading were used to evaluate the efficacy. Simultaneous recordings of RM6240C multi-channel biological signal acquisition and processing system Convulsive rats EcoG, analysis of anticonvulsant effect and its effect on EcoG after gavage AMC (25.0,100.0 mg.kg-1). Immunohistochemistry was used to determine the changes of GABA and GABAB receptor protein in the cortex and hippocampus. Results Both doses of AMC significantly reduced seizure onset and epileptiform EEG in rats (P <0.01). The levels of GABA in the cortex and hippocampus in AMC group were significantly higher than those in normal group and model group (P> 0.05). The expression of GABAB receptor protein in the hippocampus was increased (P <0.05), while the expression in the cortex was higher than that in the model group (P> 0.05). The levels of GABA and GABAB receptor protein in cortex and hippocampus of VPA group and high-dose AMC group were significantly increased (P <0.05). Conclusion AMC can antagonize PIC seizures and inhibit the epileptic discharge. The mechanism of anticonvulsant effect is related to increasing GABA content and GABAB receptor expression in cortex and hippocampus.