基础医学与临床 ›› 2007, Vol. 27 ›› Issue (11): 1208-1213.

• 研究论文 • 上一篇    下一篇

发作与卡马西平对海人酸癫痫大鼠模型耐药性的影响

吴春春 丁成赟 徐群渊 孙晓红 段德义   

  1. 首都医科大学神经科学研究所 首都医科大学天坛医院神经内科 首都医科大学神经科学研究所 首都医科大学神经科学研究所 首都医科大学神经科学研究所
  • 收稿日期:2007-03-05 修回日期:2007-04-18 出版日期:2007-11-25 发布日期:2007-11-25
  • 通讯作者: 段德义

Effects of Seizure and Carbamazepine on Multidrug Resistance in a Rat Model of Kainate-induced Epilepsy

  

  • Received:2007-03-05 Revised:2007-04-18 Online:2007-11-25 Published:2007-11-25

摘要: 摘要:目的 探讨癫痫发作和(或)抗癫痫药物卡马西平(CBZ)对多药耐药基因编码的P-糖蛋白(P-glycoprotein,P-gp)表达的影响 方法 分别给雌性SD 大鼠侧脑室注射海人酸(KA)和(或)口服CBZ药物或PBS。成模或给药后3 d、5 d、7 d、14 d、21 d和28 d灌杀大鼠取脑,用免疫组化和双标免疫染色技术对脑中P-gp进行半定量及定位分析。尼氏染色观察海马神经元的变化。结果 模型大鼠脑电图及行为变化与人类癫痫相似,CBZ对发作没有干预效果。单纯发作后第5 d 脑内P-gp表达水平增加,7 d时最高(P<0.001),14 d时仍较高(P<0.05),21 d后恢复到正常水平。阳性产物主要位于海马的毛细血管内皮细胞,也见于皮层的毛细血管及神经元。CBZ对正常大鼠P-gp的表达没有影响。CBZ+KZ组动物海马P-gp的表达与KA组动物相似,但7 d时其表达明显增强。结论 癫痫发作可诱导P-gp的表达;发作与药物可能都参与了P-gp的高表达。

关键词: 难治性癫痫, P-糖蛋白, 海人酸, 卡马西平

Abstract: Abstract: Objective To investigate the effects of seizure and/or an antiepileptic drug Carbamazepine (CBZ) on expression of P-glycoprotein (P-gp) encoded by a multidrug resistance gene. Methods Female SD rats were intracerebroventricularly injected with kainate (KA) and/or orally administered with CBZ or PBS. The animals were deeply anesthetized and perfused 3 d, 5 d, 7 d, 14 d, 21 d and 28 d after seizure or 7 d, 14 d, 21 d and 28 d after CBZ administration, and their brain was removed. Immunohistochemistry and double lebeling immunostaining were used for semiqualification analysis and location of P-gp in the brain, and Nissl staining was used to observe neuronal alterations in the hippocampus. Results The changes in EEG and behavior in the model rats were the same as those in human epilepsy. CBZ was weakly against the seizure generated by KA. Five days after seizure, P-gp expression in the hippocampus began to increase significantly and reached to its peak level at 7 d (P<0.001), then returned to the control level 21 d later. The immunopositive products were mainly present in the capillary endothelia in the hippocampus and also in the endothelia and neurons in the cortex. CBZ interference showed no effects on expression of P-gp compared with those in the PBS-injected rats. The changes in P-gp expression in KA+CBZ group were the same as those observed in the KA model rat, however, its P-gp expression at 7 d was stronger than that in the KA group. Conclusions Seizure may induce over-expression of P-gp, and CBZ may be involved in up-regulation of P-gp expression in the KA model rat.

Key words: Intractable epilepsy, P-glycoprotein, Kainate, Carbamazepine