摘要
目的:研究药物转运蛋白P-糖蛋白(P-gp)是否介导拉莫三嗪(LTG)在血脑屏障上的转运过程。方法:通过原代培养的大鼠脑微血管内皮细胞模型进行LTG摄取和外排实验,HPLC法测定单用LTG和合用能量抑制剂叠氮化钠(NaN3),P-gp调节剂环孢素A(CsA)、维拉帕米(Ver)及丙磺舒(PBD)时各组细胞内LTG的量。结果:LTG细胞摄取过程具有时间和浓度依赖性的特点。合用NaN3、CsA、Ver和PBD,均能显著增加LTG稳态摄取量,降低LTG外排量。结论:P-gp参与了LTG在血脑屏障上的转运过程。
Aim: To investigate whether the transport of lamotrigine (LTG) across the blood brain barrier (BBB) could be mediated by P-glycoprotein (P-gp) in vitro. Methods: The primary cultured rat microvascular endothelial cells (rBMECs) were introduced as an in vitro BBB model. Experiments were conducted to examine time- and concentration-dependent patterns of LTG uptake, and the effect of tested agents on the steady-state uptake of LTG. Efflux of LTG was also measured in the presence or absence of tested agents. Results: The uptake of LTG was in a time-andconcentration-dependent manner. P-gp modulators ( cyclosporin A, verapamil, probenecid) and metabolic inhibitor (sodium azide) significantly increased the steady-state uptake of LTG, and decreased the efflux of LTG. Conclusion: P-gp may contribute to the efflux transport of LTG across the BBB.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2008年第3期248-252,共5页
Journal of China Pharmaceutical University
基金
国家自然科学基金资助项目(No30672499)
江苏省药物代谢动力学重点实验室资助项目(NoBM2001201)
关键词
血脑屏障
P-糖蛋白
拉莫三嗪
环孢素A
blood brain barrier
P-glycoprotein
lamotrigine
cyclosporin A