应用MDCK-MDR1细胞模型研究3-乙酰基-11-羰基-b-乙酰乳香酸经血脑屏障的通透性  

Study on the permeation of acetyl-11-keto-beta-boswellic acid through blood-brain barrier by MDCK-MDR1 cell model

作　　者：慈小燕[1] 夏媛媛[2] 曾勇[2] 伊秀林[2] 高晶[2] 李薇[2] 司端运[2] 

机构地区：[1]天津中医药大学,天津300193 [2]天津药物研究院释药技术与药动学国家重点实验室,天津300193

出　　处：《中国新药杂志》2013年第10期1125-1129,共5页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2012ZX09304002);国家973项目(2010CB735602)

摘　　要：目的:考察3-乙酰基-11-羰基-b-乙酰乳香酸(AKBA)经血脑屏障的通透性。方法:采用MD-CK-MDR1细胞单层模型研究AKBA的双向跨膜转运,采用LC-MS/MS分析方法测定AKBA的浓度,计算其表观渗透系数(Papp)。结果:咖啡因吸收方向Papp为(18.65±1.94)×10-6cm.s-1,罗丹明123外排率(RE)为19.96,接收室HBSS中可以检测到AKBA,且AKBA的RE<2。结论:MDCK-MDR1模型的形态、通透性、P-糖蛋白功都与血脑屏障相似。AKBA不是P-糖蛋白的底物,主要通过被动扩散透过血脑屏障,但透过率比较低。Objective ： To research the permeation of acetyl-11-keto-beta-boswellic acid （AKBA） through blood-brain barrier. Methods： MDCK-MDR1 cell monolayer model was used to study the bi-directions transport of AKBA; the concentration of AKBA was measured by LC-MS/MS and apparent permeability coefficient （Papp） was calculated. Results： The Papp of caffeine and RE of rhodamine were （ 18.65 ± 1.94） ×10-6 cm· s-1 and 19.96, respectively. AKBA was detected in the receiving chamber with RE 〈 2. Conclusion： MDCK-MDR1 model is high- ly similar to blood-brain barrier in terms of conformation, permeability and P-gp functions. Although AKBA was demonstrated to be able to penetrate blood-brain barrier though passive diffusion, the penetration rate was very low, suggesting that AKBA might not be the substrate of P-gp.

关 键 词：MDCK-MDR1细胞 血脑屏障 P-糖蛋白 表观渗透系数 

分 类 号：R969.1[医药卫生—药理学]