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目的 建立局限性癫痫动物模型,探讨多药耐药基因产物P-糖蛋白的表达规律以及癫痫耐药机制。方法 42只Wistar大鼠随机分为对照组,海人酸致痫组,苯妥英钠(phenytoin sodium,PHT)+苯巴比妥(phenobarbital,PB)和加巴喷丁(gabapentin)抗癫痫药物干预组。致痫组大鼠于右侧海马区注射海人酸,于给药后第6h、24h、3d、5d和7d处死;干预组大鼠在注射海人酸前30min,分别行加巴喷丁(20mg/kg)或PHT(3～90mg/kg)+PB(30mg/kg)腹腔注射,然后注射海人酸,给药后第6h、3d、5d和7d处死。所有动物均采用免疫组织化学法检测多药耐药基因-1的表达产物P-糖蛋白。结果 对照组大鼠无癫痫发作。致痫组大鼠均出现癫痫发作,经抗癫痫药物干预的大鼠,癫痫发作的开始时间延迟、持续时间缩短(P<0.01)。不同剂量PHT组大鼠癫痫发作开始和持续时间有所不同,组间比较差异有显著性意义(P<0.01);随PHT剂量的增加,P-糖蛋白表达增高。干预组阳性细胞数高于致病组(P<0.01)。注射海人酸后6h,出现P-精蛋白强烈表达,3～5d后减弱,7d后完全消失;但干预组大鼠,在给药后第3d仍强烈表达,并逐渐增强,直至第7d仍无减弱趋势。结论 (1)一侧海马区注射海人酸,可成功地建立癫痫模型;(2)抗癫痫药物可使多药耐药基因-1的表达产物P-糖蛋白表达增强,且随药物剂量增加而
OBJECTIVE: To establish an animal model of limited epilepsy and investigate the expression of multidrug resistance gene product P-glycoprotein and the mechanism of epilepsy resistance. Methods Forty - two Wistar rats were randomly divided into control group, epilepsy group treated with kainate, phenytoin sodium (PHT) + phenobarbital (PB) and gabapentin antiepileptic group. Rats in epileptogenic group were injected with HA at the right hippocampus, and were sacrificed at 6h, 24h, 3d, 5d and 7d after administration. Rats in the intervention group were treated with gabapentin (20mg / kg ) Or PHT (3 ~ 90mg / kg) + PB (30mg / kg) were injected intraperitoneally. Then, kainate was injected, and sacrificed at 6h, 3d, 5d and 7d after administration. Immunohistochemistry was used to detect the expression of multidrug resistance gene-1, P-glycoprotein, in all animals. Results The control group rats without epileptic seizures. Epileptic seizures were observed in epileptic rats. The onset of seizures was delayed and the duration of epilepsy was shortened (P <0.01) in rats treated with antiepileptic drugs. The onset and duration of epileptic seizures of rats in different doses of PHT group were different, with significant difference between the two groups (P <0.01). The expression of P-glycoprotein increased with the increase of PHT dose. The number of positive cells in the intervention group was higher than that in the pathogenic group (P <0.01). After injection of kainic acid for 6h, P-protamine was strongly expressed, which was weakened after 3 ~ 5d and completely disappeared after 7d. However, the rats in the intervention group were still strongly expressed on the 3rd day after administration and gradually increased until the 7th day No weakening trend. Conclusion (2) Epilepsy model can be successfully established by injecting kainic acid into the hippocampus of the side. (2) Antiepileptic drugs can enhance the expression of P-glycoprotein, which is the expression product of multidrug resistance gene-1, and