中文摘要：

目的研究甘草次酸18位差向异构体即18a·甘草次酸（O／一GA）、18β-甘草次酸（β-GA）对P-糖蛋白（P-gP）底物罗丹明123在Caco-2细胞上跨膜转运的影响。方法采用MTT法检测不同摩尔浓度的18β-甘草次酸、18β-甘草次酸及维拉帕米对Caco-2细胞生长抑制作用；建立Caco-2单层细胞模型，以P-糖蛋白底物罗丹明123（Rho-123）为荧光探针，评价甘草次酸18位差向异构体和P-糖蛋白抑制剂维拉帕米对罗丹明123在Caco-2细胞上跨膜转运的影响。罗丹明123浓度采用酶标仪检测。结果高浓度（10LLmol·L。）18β-甘草次酸瞬时作用于Caco-2细胞单层模型，或者干预单层模型72h后，均使罗丹明123单位面积BL—AP侧累积转运量（transportB．A）增加，外排率（ER）增大，诱导β-糖蛋白底物罗丹明123外向转运；高浓度（10μmol·L-1）18β-甘草次酸瞬时作用于Caco-2细胞单层模型没有表现出诱导作用，但在干预Caco．2单层模型72h后，表现出对罗丹明123外向转运的诱导；各实验药物均没有对罗丹明123AP—BL侧转运产生影响。结论跨膜转运实验结果表明，18β-甘草次酸、18β-甘草次酸能诱导P-糖蛋白的外向转运，加速P-糖蛋白底物的外排，可能是甘草酸制剂增强肝脏解毒的机制之一。

英文摘要：

OBJECTIVE To study the effects of C-18 epimers of glycyrrhetinic acid, 18α-glycyrrhetinic acid （α-GA） and 18β- glycyrrhetinic acid（β-GA）, on membrane transport of P-gp substrate rhodamine 123 in Caco-2 cell monolayers. METHODS MTF assay was applied to determine the maximum non-cytotoxic dose of α-GA,β-GA and verapamil to ensure the activity of the cells during the test and to consult the maximum test concentration of each drug; appropriate Caco-2 monolayers were established in TranswellTM plates. ELISA Reader was applied to detect the concentration of Rho-123 in transfer fluid. The bi-directional transport of Rho-123 after being treated by instantaneous action and incubation with α-GA and β-GA for 72 h was studied. RESULTS High concentration （ 10μmol· L-1） of α-GA induced the efflux of Rho-123 both in the instantaneous action test and the incubation test. High concentration （ 10β-mol· L-1 ） ofβ-GA induced the efflux of Rho-123 only in the incubation test. The transport from AP to BL was not affected by any test drugs. CONCLUSION The results of the transport experiments of P-gp substrates in Caco-2 monolayers indicated that α-GA and α-GA can induce the efflux function of P-gp and accelerate the excretion of P-gp substrates. It may be one of the mechanisms of that glycyrrhizin preparation enhances liver detoxification.