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

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.