芍药苷-6-O′-苯磺酸酯在Caco-2细胞模型中吸收机制研究  

Study on absorption mechanism of paeoniflorin-6'-O-benzene sulfonate(CP-25) in Caco-2 cells

作　　者：王剑 王春[1] 肖峰[1] 马勇[1] 魏伟[1] Wang Jian;Wang Chun;Xiao Feng(Dept of Clinical Pharmacology of Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine of Education Ministry,Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine,Hefei 230032)

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,抗炎免疫药物安徽省协同创新中心,合肥230032

出　　处：《安徽医科大学学报》2018年第11期1751-1756,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号：81330081、81302845)；安徽省转化医学研究院科研基金(编号：2017zhyx33)

摘　　要：目的考察芍药苷-6-O'-苯磺酸酯(代号CP-25)在Caco-2细胞模型中吸收和转运机制。方法体外培养人结肠癌细胞Caco-2,建立高效液相色谱方法(HPLC)测定细胞模型中顶端侧(AP侧)和基底侧(BL侧)中CP-25的浓度并计算表观渗透系数(Papp)和表观渗透比(PDR);考察不同浓度和温度对CP-25转运的影响;分别考察P-糖蛋白(P-gp)抑制剂GF120918、多药耐药蛋白2(MRP2)抑制剂MK571和乳腺癌耐药蛋白(BCRP)抑制剂KO143对CP-25在Caco-2细胞吸收的影响。结果 CP-25(5、10、20μg/ml)从AP侧到BL侧的Papp值随着浓度的增加而增加;在2、5、10、20μg/ml浓度范围内,CP-25的吸收随着浓度的增加而增加,各浓度CP-25 PDR值均小于1. 5;在4℃条件下,CP-25 Papp值与37℃条件下的Papp值相比显著降低; GF-120918和MK571可显著降低CP-25从BL侧到AP侧的Papp值,显著提高从AP侧到BL侧的Papp值; KO143对CP-25双向转运Papp值无影响。结论 CP-25主要吸收机制是被动转运,可能存在主动转运的参与; CP-25是P-gp、MRP2的底物,但并不是BCRP转运蛋白的底物。Objective To investigate the mechanism of CP-25 absorption and transport in the Caco-2 cell model.Methods Human colon cancer Caco-2 cell line was cultured in vitro.The effect of concentration and temperature on the transport of CP-25 was investigated.A high-performance liquid chromatography(HPLC)methodology was established to detect the concentration of CP-25 in the apical side(AP side)and basolateral side(BL side)and calculate their apparent permeability coefficient(P app)and apparent permeability ratio(PDR).The effects of different concentration,temperature on CP-25 transport in Caco-2 cells were investigated.The effects of P-glycoprotein(P-gp)inhibitor GF120918,multidrug resistance-associate protein 2(MRP2)inhibitor MK571 and breast cancer resistance protein(BCRP)inhibitor KO143 on CP-25 transport in Caco-2 cells were investigated.Results The P app value of CP-25(5,10,20μg/ml)from AP surface to BL surface increased with the increasing of concentration;Absorption of CP-25 increased with the concentration increasing(2,5,10,20μg/ml)and all groups of PDR were less than 1.5.The P app value of CP-25 significantly decreased at 4℃when compared with the P app value of CP-25 at 37℃.GF120918 and MK571 could significantly decrease the P app value of CP-25 transport from the BL side to the AP side and significantly increase the P app value of CP-25 transport from the AP side to the BL side,KO143 has no obvious effect on the bidirectional transport of CP-25.Conclusion Passive transport is the main mechanism of CP-25 absorption,active transport may also be involved.CP-25 is P-gp and MRP2 substrates,but not BCRP substrates.

关 键 词：芍药苷-6′-O-苯磺酸酯 P-糖蛋白 CACO-2细胞 吸收机制 

分 类 号：R917[医药卫生—药物分析学]