目的　了解常用抗癫痫药 (AED)对大鼠大脑皮质星形胶质细胞多药耐受基因 (MDR1)的诱导作用 ,探讨难治性癫痫的耐药机制。方法　给予不同浓度的苯巴比妥钠 (PB)、苯妥英钠(PHT)、卡马西平 (CBZ)和丙戊酸钠 (VPA)持续作用于培养的新生鼠大脑皮质星形胶质细胞 ,分别在给药后 10、2 0和 30d ,用免疫细胞化学法检测MDR1的标志物P 糖蛋白 (Pgp)的表达率。结果　无药物作用的正常星形胶质细胞Pgp的表达率在各时点均小于 5 % ;低浓度组各药在各时点Pgp的表达率与对照组比较差异无显著意义 ;有效血药浓度组仅PB 2 0mg/L、PB 40mg/L和PHT 2 0mg/L在 30d时Pgp表达增强 ;给药后 10d ,高浓度组各药Pgp表达率无明显增高 ;2 0d时PB、PHT和VPA组Pgp表达增强 ;30d时 4种AED均有Pgp表达增强。结论　AED可以诱导MDR1表达增强 ,且与剂量和时间相关。AED诱导的MDR1表达增强可能参与了难治性癫痫的形成 Objective To investigate the induction of multidrug resistance gene (MDR1) by commonly used antiepileptic drugs (AEDs) on cerebral cortex astrocytes in rats and explore the mechanism of drug resistance in refractory epilepsy. Methods PBMCs, PHT, CBZ and VPA were administered continuously to cultured cortical astrocytes of neonatal rats, respectively. The expression of Pgp, a marker of MDR1, was detected by immunocytochemistry at 10, 20 and 30 d after administration. Results The expression of Pgp in normal astrocytes with no drug effect was less than 5% at all time points. There was no significant difference in the expression of Pgp at various time point between low concentration group and control group. The effective plasma concentration The expression of Pgp in PBMCs at 0 mg / L, PB 40 mg / L and PHT at 20 mg / L was enhanced at 30 d, but no significant increase at 10 d after administration. PB, PHT and VPA Group Pgp expression enhanced; 30d when the four AED Pgp expression increased. Conclusion AED can induce MDR1 expression increased, and with dose and time related. AED-induced enhancement of MDR1 expression may be involved in the formation of refractory epilepsy