芒果苷在Caco-2细胞模型中转运机制的研究  

Transport Mechanism of Mangiferin in Caco-2 Cell Model

作　　者：陈宝婷[1] 陈举亮 孙毅东[1] 詹亚坤[1] 刘奕明 CHEN Baoting;CHEN Juliang;SUN Yidong;ZHAN Yakun;LIU Yiming(Zhuhai Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine,Zhuhai 519015 Guangdong,China;Phase I Clinical Trial Center of The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120 Guangdong,China;Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome,Guangzhou 510120 Guangdong,China)

机构地区：[1]广东省中医院珠海医院药剂科,广东珠海519015 [2]广州中医药大学第二附属医院Ⅰ期临床研究室,广东广州510120 [3]广东省中医证候临床研究重点实验室,广东广州510120

出　　处：《中药新药与临床药理》2022年第9期1248-1253,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省科技计划项目(2017B030314166,2014A020221115)。

摘　　要：目的采用人结肠癌上皮细胞单层模型(Caco-2细胞模型)研究芒果苷在小肠吸收转运的特性,探讨芒果苷的口服吸收机制。方法采用Caco-2细胞模型进行芒果苷的跨膜转运实验,探讨时间、pH值、浓度、外排转运蛋白P-糖蛋白(P-gp)抑制剂、多药耐药相关蛋白2(MRP2)抑制剂、乳腺癌耐药蛋白(BCRP)抑制剂对芒果苷转运的影响。结果芒果苷在Caco-2细胞模型上的转运具有时间依赖性,不同浓度芒果苷在Caco-2细胞的表观渗透系数(P_(app))无显著性差异,微绒毛面顶侧(AP)到底侧(BL)的P(app(AP→BL))为(8.33±1.99)×10^(-6)~(8.48±1.15)×10^(-6)cm·s^(-1),BL侧到AP侧的P_(app(BL→AP))为(29.19±3.64)×10^(-6)~(33.20±5.72)×10^(-6)cm·s^(-1),P_(app(BL→AP))明显大于P(app(AP→BL))(P<0.05),药物外排率(ER)大于3;芒果苷的P_(app)随pH的增加而显著性增加;P-gp抑制剂维拉帕米(P<0.001)和环孢素A(P<0.05)能显著增加芒果苷AP→BL方向的表观渗透系数;MRP2抑制剂MK571显著减少芒果苷两侧表观渗透系数(P<0.01);BCRP抑制剂白杨素和烟曲霉素C对芒果苷的转运无明显影响。结论芒果苷为中等吸收药物,碱性环境有利于其转运,在Caco-2细胞模型上的转运方式以被动扩散为主,并存在主动转运,不受外排蛋白BCRP的影响,但与P-gp有关,MK571与芒果苷可能存在竞争转运。Objective To investigate the transport characteristics of mangiferin in Caco-2 cell model and to clarify the oral absorption mechanism of mangiferin.Methods Effects of time,pH,concentration,P-gp inhibitor,MRP2inhibitor,and BCRP inhibitor on the transportation of mangiferin in Caco-2 cell model were investigated.Results The transport of mangiferin in Caco-2 cell model was time dependent but P_(app) of mangiferin showed no difference in concentration,P_(app)(AP→BL)was(8.33±1.99)×10^(-6)cm·s^(-1)to(8.48±1.15)×10^(-6)cm·s^(-1)and P_(app(BL→AP))was(29.19±3.64)×10^(-6)cm·s^(-1)to(33.20±5.72)×10^(-6)cm·s^(-1);P_(app(BL→AP))was significant higher than Papp(AP→BL)(P<0.05)and ER was more than 3.The P_(app) of mangiferin increased significantly with the increase of pH.P-gp inhibitors,verapamil(P<0.001)and cyclosporine A(P<0.05)obviously increased the P_(app)(AP→BL)of mangiferin.MRP2 inhibitor MK571 decreased bidirectional P_(app) of mangiferin markedly(P<0.01).BCRP inhibitor chrysin and Fumitremorgin C had no effect on P_(app) of mangiferin.Conclusion Mangiferin was well absorbed and alkaline environment was favorable for its transport.Passive diffusion was the main absorption mechanism of mangiferin and a cellular efflux system was participated.P-gp would influence the transport of mangiferin while BCRP not MK571 and mangiferin may have competitive translocation.

关 键 词：芒果苷 CACO-2细胞 转运 P-糖蛋白 多药耐药相关蛋白2 

分 类 号：R285.5[医药卫生—中药学]