大鼠耐苯妥英钠和苯巴比妥钠杏仁核点燃模型及多药耐受基因的表达

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

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。

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.