苯妥英钠、苯巴比妥钠诱导建立难治性癫(癎)动物模型

目的探索性应用苯妥英钠（PHT）、苯巴比妥钠（PB）诱导建立难治性癫痫动物模型，并研究其多药耐药机制。方法将60只大鼠随机分为实验组50只和对照组10只；实验组给予亚抽搐剂量戊四氮腹腔注射，其中45只大鼠确定点燃．将其随机分为给药组35只和未给药组10只。给药组应用较大剂量PHT、PB腹腔注射，其间注射小剂量戊四氮．根据Racine行为分级以及脑电图改变，从中筛选出耐PHT和PB的难治性癫痫动物模型。应用免疫组化法观察比较P糖蛋白（Pgp）在各组脑组织中的表达。结果12只大鼠制成难治性癫痫动物模型（耐药组），11只为药物有效组，12只死亡。耐药组大鼠脑组织Pgp表达较对照组、未给药组和药物有效组增强，差异有高度统计学意义（P〈0．01）。结论应用较大剂量PHT和PB诱导点燃大鼠制作难治性癫痫的动物模型．方法可行。该模型可以用于研究难治性癫痫脑内PgP的表达。PgP的高表达与难治性癫痫发生密切相关。

The establishment of animal model of refractory epilepsy induced by phenytoin and phenobarbital sodium

Objective To establish an animal model of refractory epilepsy by peritoneal injection of phenytoin sodium(PHT) and phenobarbital sodium(PB),and investigate into their multidrug resistance mechanism in kindling rats.Methods Sixty Wistar rats were randomly divided into two experimental groups(50 rats) and control group(10 rats).The experimental group rats were kindled by repeated peritoneal injection of sub-convulsive dose of pentylenetetrazol(PTZ).The 45 kindled rats were randomly divided into treatment group(35 rats) and non-treatment group(10 rats).Treatment group rats were injected with large doses of PHT and PB.The PHT-PB resistant rats were selected from treatment group by Racine scale and the EEG change after peritoneal injection of low dose of PTZ.P-glycoprotein(Pgp) expressions in the brain tissues were compared by immunohistochemical method.Results Twelve rats were selected as the animal model of refractory epilepsy(resistant group),11 were classified to drug-effective group,and 12 died.The expression of PGP in the brain tissue was significantly higher in the PHT-PB resistant rats than in control group,non-treatment group and drug-effective group(P<0.01).Conclusion It is feasible to make the animal model of refractory epilepsy by peritoneal injection of large dose of PHT and PB in kindled rats.The model can be used to investigate the expression of Pgp in the brain of refractory epilepsy rats.The high expression of Pgp has an intimate relation with genesis of refractory epilepsy.