3-乙酰基-11-羰基-β-乙酰乳香酸在Caco-2和MDCK细胞模型中的吸收研究  

Absorption of 3-acetyl-11-keto-β-boswellic acid in Caco-2 cells and MDCK cell models

作　　者：慈小燕[1] 夏媛媛[2] 曾勇[2] 伊秀林[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代动力学国家重点实验室,天津300193

出　　处：《中草药》2013年第9期1162-1167,共6页Chinese Traditional and Herbal Drugs

基　　金：国家"重大新药创制"科技重大专项-新药临床前药物代谢动力学技术平台建设(2012ZX09304002);国家"973"项目(2010CB735602)

摘　　要：目的研究乳香提取物中3-乙酰基-11-羰基-β-乙酰乳香酸(AKBA)在Caco-2、MDCK-MDR1和MDCK-Wild细胞模型中的吸收转运机制。方法利用Caco-2、MDCK-MDR1和MDCK-Wild细胞模型,研究AKBA由细胞层顶端(AP)→基底端(BL)和BL→AP的双向转运过程;采用LC-MS/MS法测定AKBA的量,计算表观渗透系数(Papp)。结果在Caco-2细胞模型中,50μmol/L AKBA由AP→BL、BL→AP的Papp分别为7.9×10 7、1.5×10 7cm/s,在MDCK-MDR1细胞模型中,50μmol/LAKBA由AP→BL、BL→AP的Papp分别为2.6×10 7、0.8×10 7cm/s,在MDCK-Wild细胞模型中,50μmol/LAKBA由AP→BL、BL→AP的Papp分别为2.4×10 7、0.6×10 7cm/s,3种细胞模型中外排率均小于2。结论 AKBA在肠道中吸收不良,不是P-糖蛋白的底物,推测其通过摄入型主动转运和被动扩散两种机制透过小肠上皮细胞。Objective To study the mechanisms of absorption and transport of 3-acetyl-ll-keto-β-boswellic acid （AKBA） from Boswellia carterif in Caco-2 cell, MDCK-MDR1, and MDCK-Wild cell models. Methods The Caco-2, MDCK-MDR1, and MDCK-Wild cell monolayer models were used to study the bi-directional transport of AKBA in apical （AP）→basal （BL） or BL→AP; The concentration of AKBA was measured by LC-MS/MS and apparent permeability coefficient （Papp） was calculated. Results Papp （AP→BL） and Papp （BL→AP） values of AKBA （50μmol/L） in Caco-2 cell model were 7.9 × 10ˉ^7 and 1.5 × 10ˉ^7cm/s, respectively; Papp （AP→BL） and Papp （BL→AP） values of AKBA （50μmol/L） in MDCK-MDR1 cell model were 2.6 × 10-7 and 0.8 × 10ˉ^7 cm/s, respectively; Papp （AP→BL） and Papp （BL→AP） of AKBA （50μmol/L） in MDCK-Wild cell model was 2.4 × 10ˉ^7 and 0.6 × 10ˉ^7 cm/s, respectively; The rates of effiux （Rε） for AKBA in Caco-2 and MDCK-MDR1 cell monolayers were both smaller than 2, Conclusion AKBA is not the substrate of P-gp and its absorption rate is low. AKBA is absorbed through the intestinal epithelial cells by active transport absorption and passive diffusion possibly.

关 键 词：乳香 3-乙酰基-11-羰基-β-乙酰乳香酸 CACO-2细胞 MDCK-MDR1 MDCK-Wild 转运机制 吸收特性 P-糖蛋白 

分 类 号：R286.3[医药卫生—中药学] R285.5[医药卫生—中医学]