马钱子生物碱类成分在MDCK-MDR1单层细胞模型中的转运机制研究  

Study on transport mechanism of brucine and strychnine in MDCK-MDR1 cell monolayer model

作　　者：胡亚 刘运锋 朱卫丰 陈丽华 管咏梅 金晨 HU Ya;LIU Yun-feng;ZHU Wei-feng;CHEN Li-hua;GUAN Yong-mei;JIN Chen(Key Laboratory of Modem Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of TCM,Nanchang 330004,China)

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室

出　　处：《中草药》2019年第12期2876-2883,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81760717);国家自然科学基金资助项目(81460606);江西省中药学一流学科专项科研基金项目(JXSYLXK-ZHYAO048)

摘　　要：目的研究马钱子碱、士的宁在MDCK-MDR1单层细胞模型中的双向转运机制。方法 MTT法确定马钱子碱、士的宁对MDCK-MDR1单层细胞毒性范围,以MDCK-MDR1单层细胞为体外研究模型,考察转运时间、药物作用质量浓度、P-糖蛋白(P-gp)抑制剂维拉帕米对马钱子碱、士的宁的累积吸收浓度(Ccum)和表观渗透系数(Papp)的影响。结果马钱子碱和士的宁Papp均> 1×10^-5 cm/s,Papp(BL→AP)/Papp(AP→BL)均<2。马钱子碱、士的宁与维拉帕米合用,显著降低了Papp(BL→AP)/Papp(AP→BL)值。结论马钱子碱、士的宁以被动转运为主,P-gp抑制剂维拉帕米对其吸收有明显抑制作用,马钱子碱、士的宁可能是P-gp底物。Objective To study the bi-direction transport behavior of brucine and strychnine in the MDCK-MDR1 cell monolayer model. Methods MTT method was employed to confirm the safe concentration of brucine and strychnine towards MDCK-MDR1 cells. The effects of transport time, drug concentration, and P-glycoprotein inhibitor verapamil on cumulative absorption concentration (Ccum) and apparent permeability coefficient (Papp) of brucine and strychnine in MDCK-MDR1 monolayer cells were studied. Results The Papp value of brucine and strychnine was larger than 1×10^-5 cm/s and the ratio of Papp(BL→AP) vs Papp(AP→BL) was less than 2. Brucine/strychnine combined with verapamil decreased the ratio of Papp(BL→AP) vs Papp(AP→BL). Conclusion The absorption of brucine and strychnine in MDCK-MDR1 cell monolayer model was well and the passive transference was its main intestinal absorption mechanism. The P-gp inhibitor verapamil has a significant inhibitory effect on brucine and strychnine absorption. Brucine and strychnine may be a substrate of P-glycoprotein.

关 键 词：马钱子碱 士的宁 MDCK-MDR1单层细胞模型 双向转运 P-糖蛋白 

分 类 号：R285.61[医药卫生—中药学]