摘要
目的观察多药耐药蛋白(multidrugresistance-associatedprotein,MRP)拮抗剂丙磺舒对大鼠大脑皮层细胞外液卡马西平和苯妥英钠含量的影响,证明MRP能够减少皮层内抗癫痫药物的浓度,探讨脑内表达MRP和难治性癫痫多药耐药的关系。方法在健康大鼠大脑皮层内安置微透析探针,腹腔注射卡马西平(20mg/kg)和苯妥英钠(50mg/kg),在给药后不同时间点收集透析液,并用高效液相检测其中的药物浓度,通过微透析探针局部给于丙磺舒,观察后者能否提高大鼠大脑皮层细胞外液卡马西平和苯妥英钠的浓度。结果丙磺舒升高了皮层细胞外液中卡马西平和苯妥英钠的药物浓度,前者在给药后45min～120min显著增高(P<0.05),后者在给药后30min～150min显著增高(P<0.05)。结论MRP具有限制卡马西平和苯妥英钠通过血脑屏障的作用,引起抗癫痫药物在大鼠大脑皮层细胞外液中分布减低,MRP表达增加可能参与了难治性癫痫多药耐药机制的形成。
Objective To study the effect of inhibitor of multidrug resistance-associated protein (MRP) probenecid in the regulation of concentration of carbamazepine and phenytoin in the extracellular fluid of cerebral cortex of rat,to indicate that MRP decrease the concentration of antiepileptic drug in extracellular fluid of cerebral cortex and deduce whether expression of MRP in brain is involved in multidrug resistance mechanisms of refractory epilepsy.Methods We placed the microdialysis probe into the cortex of rats,after systemic injection of carbamazepine and phenytoin,dialysate were collected and the antiepiletic drug concentration in the extracellular fluid of the cerebral cortex were determined by high-performance liquid chromatography(HPLC).Then observing whether the concentration of antiepileptic drugs in extracellular fluid can be enhanced by MRP's inhibitor probenecid.~Results Probenecid significantly increased the concentration of carbamazepine in extracellular fluid during 45min～120min after injection(P<0.05),phenytoin was also enhanced during 30min～150min after injection(P<0.05).Conclusion Penetration of carbamazepine and phenytoin through blood-brain barrier are restricted by MRP.MRP decreased the antiepiletic drug concentration in the extracellular fluid of the cerebral cortex.So increased expression of MRP in brain may be involved in the mechanisms of multidrug resistance of refractory epilepsy.
出处
《中风与神经疾病杂志》
CAS
CSCD
北大核心
2004年第6期489-492,共4页
Journal of Apoplexy and Nervous Diseases
基金
国家自然科学基金资助项目(30370511)
上海市引进海外高层次留学人员专项基金资助项目(2004-1-5)
