出 处:《中国药学杂志》2011年第4期270-274,共5页Chinese Pharmaceutical Journal
基 金:山西省自然科学基金资助课题(NO20041109);山西医科大学创新基金资助课题(01200804)
摘 要:目的研究胺甲氧斑蝥素(AMOC)对电刺激大鼠坐骨神经和青霉素(PNC)协同诱发痫性放电模型的对抗作用及对皮层脑电图(EcoG)、诱发电位(CEP)和γ-氨基丁酸(GABA)C受体ρ2 mRNA表达的影响。方法建立电刺激坐骨神经和PNC协同诱发大鼠惊厥模型,丙戊酸钠(VPA)为阳性对照,以惊厥潜伏期和Racine痫性行为学分级作为评定药效指标,RM6240C型多道生物信号采集处理系统同步记录惊厥大鼠EcoG和CEP,观察AMOC的抗惊厥作用及对EcoG痫样波潜伏期、发放频率、最高振幅和CEP振幅的影响。采用实时荧光定量聚合酶链反应技术(RT-PCR)检测海马区GABAC受体ρ2 mRNA的表达变化。结果 AMOC和VPA均能明显延长大鼠惊厥潜伏期,减轻PNC诱发大鼠惊厥发作程度,明显延长痫性放电潜伏期,减少相同时间内痫样波发放频率,降低最高振幅和诱发电位振幅,与PNC模型组相比有显著性差异(P<0.01);PNC模型组GABAC受体ρ2 mRNA表达量较正常组下降,有统计学意义(P<0.05);AMOC和VPA组较PNC模型组明显升高,差别有统计学意义(P<0.01)。结论 AMOC和VPA均可对抗电刺激坐骨神经和PNC协同诱发大鼠惊厥发作,抑制痫性放电和诱发电位振幅,提高海马区GABAC受体ρ2 mRNA基因表达量。OBJECTIVE To investigate the effects of 4-amino-2-methoxy-cantharidinimide (AMOC) on the cerebral cortex electroencephalogram( EcoG), cerebral cortex evoked potential( CEP), and the expression of GABAc receptor ρ2 mRNA in the convulsive rat. METHODS The model of electricity stimulating the sciatic nerve and penicillin coordination (PNC)was used to induce convulsions in rats, with valproate(VPA) as the positive control. The convu]sive seizure latency and the Racine behavior study classification were considered as the index to evaluate drug efficacy. RM6240C multi-channel biological signal-gathering and processing system synchronously recorded EcoG and CEP of the convulsive rats, after intragastric AMOC (176 and 88 mg·kg^-1), and the anti-convulsion effects, the influence on the epileptiform discharge laten period, the frequency of attack, the highest amplitude and the CEP amplitude were investigated. Real time polymerase chain reaction (RT-PCR) was adopted to test the changes in the expression of hippocampus GABAc receptor p2 mRNA. RESULTS The AMOC group and the VPA group obviously prolonged the seizure latency and the epileptiform discharge laten period, lessened the degree of the convulsive seizures in rats induced by penicillin, reduced the frequency of epileptoid discharge wave within the same period of time and decreased the highest wave amplitude and the evoked potential amplitude. Compared with the PNC group, there was a significant difference( P 〈 0.01 ) , and with the normal group, the expression of the GABAc receptor p2 mRNA decreased in the PNC group with statistical significance( P 〈 0.05 ). Compared with the PNC group, the expression of the GABAc receptor ρ2 mRNA was increased significantly in the AMOC and the VPA groups(P 〈0.01 ). CONCLUSION AMOC and VPA could antagonize convulsive seizure and inhibit epileptiform discharge and the evoked potential amplitude, and could enhance the GABAcreceptor ρ2 mRNA expression in rat hippocampus area.
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