P-糖蛋白抑制剂tariquidar对黄芪甲苷在bEND.3细胞上跨膜转运的影响及机制  

Effect and Mechanism of P-glycoprotein Inhibitor Tariquidar on the Transmembrane Transport of AstragalosideⅣin bEND.3 Monolayer Cells

作　　者：张伟 朱全刚 ZHANG Wei;ZHU Quan-gang(PhaseⅠClinical Trial Center,Shanghai Skin Disease Hospital,Shanghai 200443,China)

机构地区：[1]上海市皮肤病医院Ⅰ期临床试验中心,上海200443

出　　处：《中国药学杂志》2021年第3期204-209,共6页Chinese Pharmaceutical Journal

基　　金：上海市皮肤病医院国家自然科学基金培育项目资助(17GZRPY11);上海市皮肤病医院后备导师项目资助(17HBDS03)。

摘　　要：目的研究P-糖蛋白(P-glycoprotein,P-gp)抑制剂N-[2-[[4-[2-(6,7-二甲氧基-3,4-二氢-1H-异喹啉-2-基)乙基]苯基]氨基甲酰基]-4,5-二甲氧基苯基]喹啉-3-甲酰胺(tariquidar)对黄芪甲苷(astragalosideⅣ,ASI)跨膜转运的影响及机制。方法采用bEND.3细胞模型评价P-gp抑制剂tariquidar对bEND.3细胞摄取ASI的影响,以及P-gp抑制剂tariquidar对ASI跨膜转运的影响。结果ASI浓度在10~100μmol·L^(-1)内对bEND.3细胞活性无影响。P-gp抑制剂tariquidar能够明显增加ASI在bEND.3细胞内摄取含量(P<0.05)。当加入P-gp抑制剂tariquidar后,ASI从AP→BL侧P_(app)值基本没有变化,而ASI从BL→AP侧P_(app)值明显下降(P<0.05),ASI的P_(app)(B→A)/P_(app)(A→B)从1.01降到0.55,表明ASI跨膜转运受到转运蛋白P-gp的外排作用。结论ASI跨膜转运机制为被动转运,兼有外排蛋白参与。P-gp抑制剂可以减少ASI外排进而增加ASI在组织中的渗透和吸收。OBJECTIVE To study the effect of P-glycoprotein inhibitor tariquidar on the transport of astragalosideⅣ(ASI)and the potential mechanism based on cell culture model.METHODS bEND.3 monolayer cell model was used to evaluate whether tariquidar could facilitate the net uptake of ASI into bEND.3 cells and the transport mechanism of ASI.RESULTS ASI did not affect the viability of bEnd.3 cells in the range of 10 to 100μmol·L-1.P-glycoprotein inhibitor tariquidar could significantly facilitate the net uptake of ASI into bEND.3 cells.The addition of P-glycoprotein inhibitor tariquidar did not change the apparent permeability of ASI from the apical(AP)side to the basal(BL)side.However,it significantly decreased the apparent permeability of ASI from the BL side to the AP side(P<0.05),and the P_(app)(B→A)/P_(app)(A→B)ASI from 1.01 to 0.55,which indicated that the transport ASI was influenced by P-gp.CONCLUSION The transport mechanism ASI might be passive diffusion combined with active transportation mediated by efflux protein.All of these results implicate that P-gp inhibitor can decrease the efflux of ASI from bEND.3 cells and thus increase the penetration and absorption of ASI in tissues.

关 键 词：黄芪甲苷 P-糖蛋白 小鼠脑微血管内皮细胞 跨膜转运 

分 类 号：R945[医药卫生—微生物与生化药学]