不同18α和18β-甘草酸配比对P-gp转运功能和大鼠CYP3A酶活性的影响  

Effects of Different 18α and 18β-glycyrrhizic acid Ratios of on P-gp Transport Function and CYP3A Enzyme Activity in Rats

作　　者：霍小位 王士中 孟祥波 柳亚飞 赵燕燕[1] HUO Xiao-wei;WANG Shi-zhong;MENG Xiang-bo;LIU Ya-fei;ZHAO Yan-yan(College of Pharmaceutical Science,Key Laboratory of Pharmaceutical Quality Control of Hebei Province,Hebei University,Baoding 071002,China;Hebei Qiyi Tang Pharmaceutical Co.,LTD,Baoding 071002,China)

机构地区：[1]河北大学药学院,河北省药物质量分析控制重点实验室,河北保定071002 [2]河北祁一堂药业有限公司,河北保定071002

出　　处：《现代食品科技》2018年第9期26-31,共6页Modern Food Science and Technology

基　　金：河北省自然基金项目(H2013201203);河北大学医学学科专项资金建设项目(2014A1003);河北大学研究生创新资助项目(hbu2018ss74)

摘　　要：本研究旨在探究不同配比的18α、18β-甘草酸(18α、18β-GA)对P-糖蛋白(P-gp)转运功能和大鼠CYP3A酶活性的影响。建立Caco-2细胞单层模型,通过检测接收池罗丹明123溶液的荧光强度,考察不同配比的18α、18β-GA对P-gp转运功能的影响;利用大鼠的肝脏制作微粒体,通过温孵实验检测不同浓度及不同比的18α、18β-GL对CYP3A酶活性的影响。当18α-GA和18β-GA配比为6:4时,对P-gp的抑制作用最强;当两种异构体配比为0:10时,对P-gp的诱导作用最强。18α-GA浓度在50~100μg/m L范围内,对CYP3A酶活性有明显抑制作用。18β-GA浓度在10~50μg/m L范围内,对CYP3A酶活性有明显诱导作用。在甘草酸总浓度为10μg/m L,18α、18β-GA比例为2:8时,对CYP3A酶活性的诱导作用最强,高于相同浓度的18β-GA单体。随着药物浓度及18α-GA比例增加,对CYP3A酶活性的抑制作用增强。当浓度为100μg/m L、18α与18β-GA配比为10:0时,对CYP3A酶抑制作用最强。18α、18β-GA的配比不同,对P-gp转运功能及对大鼠CYP3A酶活性的影响不同,这将为指导临床用药提供科学依据。The present study was designed to investigate the effect of different ratios of 18α-glycyrrhizic acid（18α-GA） and 18β-glycyrrhizic acid（18β-GA） on P-gp function and CYP3 A activity. A Caco-2 cell monolayers model was established. The fluorescence intensity of the rhodamine 123 solution in the receiving pool was determined to investigate the effects of different ratios of 18α-GA and 18β-GA on P-gp transport function. Microsomes were made from the liver of rats, and the effects of different concentrations and different ratios of 18α and 18β-GA on the activity of CYP3 A were analyzed after incubation. The ratio of 18α-GA and 18β-GA at 6：4 exhibited the strongest inhibitory effect on P-gp, whilst the ratio at 0：10 led to the strongest induction of P-gp. The concentration of 18α-GA in the range of 50-100 μg/m L significantly inhibited the activity of CYP3 A, whilst 18β-GA at 10-50 μg/m L significantly induced the activity of CYP3 A. The induction of CYP3 A was the strongest, when the ratio of 18α-GA and 18β-GA was at 2：8 and the total GA concentration was at 10 μg/m L. Such an induction was greater than that for 18β-GA at the same concentration. As the GA concentration and the 18α-GA to 18β-GA ratio increased, the inhibition of CYP3 A enzymatic activity was enhanced. At the 18α-GA to 18β-GA ratio of 10：0 and the total GA concentration of 100 μg/m L, the inhibition of CYP3 A enzyme was the strongest. Different ratios of 18α-GA and18β-GA exhibited different effects on P-gp transport function and CYP3 A enzymatic activity in rats, which would provide scientific basis for guiding clinical drug therapy.

关 键 词：甘草酸 细胞色素P-450 CYP3A P糖蛋白 

分 类 号：R285.5[医药卫生—中药学]