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50~100 μg/mL范围内，对CYP3A酶活性有明显抑制作用。18β-GA浓度在10~50 μg/mL范围内，对CYP3A酶活性有明显诱导作用。在甘草酸总浓度为10 μg/mL，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100 μg/mL、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 CYP3A 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 CYP3A 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/mL significantly inhibited the activity of CYP3A, whilst 18β-GA at 10~50 μg/mL significantly induced the activity of CYP3A. The induction of CYP3A 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/mL. 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 CYP3A enzymatic activity was enhanced. At the 18α-GA to 18β-GA ratio of 10:0 and the total GA concentration of 100 μg/mL, the inhibition of CYP3A enzyme was the strongest. Different ratios of 18α-GA and18β-GA exhibited different effects on P-gp transport function and CYP3A enzymatic activity in rats, which would provide scientific basis for guiding clinical drug therapy.

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）