肖争 晏勇 王学峰 重庆医科大学附属第一医院神经内科 400016 中华神经科杂志 1999 0 32 6


    关键词：疾病模型；动物；抗惊厥药；；抗药性；多药 期刊 zhsjkzz 0 论著摘要 fur -->


    

【摘要 】 目的 探索耐苯妥英钠和苯巴比妥钠(PHT-PB)杏仁核点燃大鼠模型的建立并评价其可靠性。方法 采用苯妥英钠(PHT)、苯巴比妥钠(PB)对 40只杏仁核点燃大鼠进行筛选，按照国际通用标准，根据后放电阈值(after discharge threshold, ADT )的变化判断点燃大鼠对 PHT和PB的敏感性，并测定大鼠脑部P-糖蛋白(P-glycoprotein, PGP)的表达,证实耐药的客观性。结果 点燃鼠对PHT、PB具有不同程度的敏感性，6只点燃大鼠对PHT、PB不敏感；6只点燃大鼠PHT、PB能显著增高其 ADT。耐药组鼠大脑广泛脑区的PGP表达较药物有效组显著增强。结论 用PHT、PB对点燃大鼠进行筛选以制备耐 PHT-PB点燃模型的方法是可行的；可利用其建立难治性癫痫模型，进行耐药机制的探讨

Development of PHT-PB-resistant amygdala-kindled rats and expression of MDR1

XIAO Zheng, YAN Yong, WANG Xuefeng.

    Department of Neurology,The First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400016

【 Abstract 】 Objective To study the method of development of PHT-PB-resistant amygdala-kindled rats. Methods By examining the effects of the antiepileptic drugs PHT and PB in a group of rapidly kindled rats,the 40 animals with different sensitivity to these drugs were selected. Then using immunohistochemistry method to determinate the expression of PGP in the brain of the rats. Results Using determination of the after discharge threshold for evaluation of PHT′s and PB′s anticonvulsant effects, 6 animals showed no increase in their ADT at repeated test trials with PHT or PB (from PHT-PB-resistant rats), and 6 animals exhibited reproducible increase in ADT about 100% after injection of PHT or PB (from PHT-PB-nonresistant rats). The immunohisto-chemistry for P-glycoprotein showed increased staining in capillary endothelium in the samples from PHT-PB-resistant rats as compared with staining in PHT-PB-nonresistant rats,in extensive fields of bilateral cerebral hemispheres (P<0.05). Conclusion The procedure,using PHT, PB to screening kindling models to make PHT-PB-resistant amygdala-kindled rats, would be reliable .Overexpression of PGP in PHT-PB-resistant rats would suggest that the kindled rats with PHT-PB resistance could serve as reliable models of drug resistant epilepsy.The kindled rats with PHT-PB resistance might be a resource for the investigation of the mechanisms for drug resistance in epilepsy.

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