摘要
目的研究长期使用抗癫疒间药物(AEDs)对大鼠脑中P-糖蛋白(P-gp)功能活性和表达水平的影响。方法选择苯巴比妥、苯妥英钠和卡马西平三个典型AEDs,在大鼠体内连续给药21天,然后观察脑组织中皮质和海马P-gp的改变。结果底物罗丹明123转运实验表明P-gp功能增强,进一步通过Western Blot分析表明P-gp表达增强,并用免疫组化染色显示其细胞定位在血脑屏障上。结论长期AEDs诱导可以同时导致大鼠血脑屏障上P-gp功能活性和表达水平的升高。
Objective To investigate whether chronic exposure of antiepileptic drugs(AEDs) increased P-glycoprotein(P-gp) function and expression in brain of rats.Methods Three drugs phenobarbital(PB),phenytion(PHT) and carbamazepine(CBZ) were orally given to rats for successive 21 days,P-gp activity and levels in brain was assessed.Results Tissue-to-plasma concentration ratios of Rho123 were significantly decreased in cerebral cortex and hippocampus.Immunohistochemistry result showed that up-regulation of the P-gp mainly occurred in capillary endothelial vessels.Western blot result suggested that the protein level of P-gp in cortex and hippocampus of rats exposed to drugs was significantly higher than that of control rats.Conclusion Chronic exposure of AEDs may increase P-gp function and level in brain of rats.
出处
《徐州医学院学报》
CAS
2010年第4期230-233,共4页
Acta Academiae Medicinae Xuzhou
关键词
P-糖蛋白
血脑屏障
抗癫间疒药物
诱导
P-glycoprotein
Blood-brain barrier
Antiepileptic drugs
Induction