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目的考察多成分环境下甘草次酸在大鼠肠道中的吸收特性。方法采用大鼠在体单向肠灌流模型考察多成分环境下甘草次酸在大鼠肠道中的吸收情况,HPLC法测定肠灌流收集液中甘草次酸的量,计算甘草次酸在大鼠回肠中的有效渗透系数(Peff)、吸收速率常数(Ka)和吸收分数(Fa),考察甘草次酸不同质量浓度、P-糖蛋白(P-gp)抑制剂维拉帕米,以及不同成分配伍对甘草次酸肠吸收的影响。结果 10、20μg/m L甘草次酸灌流液在回肠段的Peff、Ka和Fa值无显著差异,加入100μmol/L维拉帕米后,10μg/m L甘草次酸的Peff、Fa值增大,说明甘草次酸可能为P-gp的底物;2种成分配伍后,黄芩苷对甘草次酸肠吸收的影响最明显,使甘草次酸的Peff值由(4.05±0.78)×10-5 cm/s降低到(2.18±0.63)×10-5 cm/s,减少甘草次酸的渗透。而葛根素、小檗碱对甘草次酸渗透性无明显影响。3种成分配伍的实验结果表明,甘草次酸与葛根素、小檗碱配伍后,渗透系数未发生改变,甘草次酸与葛根素、黄芩苷配伍后渗透系数发生改变,但变化不明显,甘草次酸与黄芩苷、小檗碱配伍后,渗透性降低,Peff值由(4.05±0.78)×10-5 cm/s降低到(1.35±0.69)×10-5 cm/s,黄芩苷对甘草次酸肠吸收影响最明显。结论甘草次酸在大鼠回肠段能较好地被吸收,一定范围内的药物质量浓度对甘草次酸的Peff和Ka无明显影响,初步确定其吸收机制为被动扩散,甘草次酸是P-gp的底物,且存在转运蛋白饱和现象;黄芩苷对甘草次酸的吸收影响显著,可能是通过诱导P-gp的表达,增加了甘草次酸从细胞内到细胞外的外排,降低了甘草次酸的渗透,影响其吸收。
Objective To investigate the absorption characteristics of glycyrrhetinic acid in rat intestine under multi-component environment. Methods The rat model of intestinal perfusion was used to investigate the absorption of glycyrrhetinic acid in the intestine of rats in a multi-component environment. The content of glycyrrhetinic acid in the peritoneal perfusion fluid was determined by HPLC. The glycyrrhetinic acid (Peff), absorption rate constant (Ka) and absorption fraction (Fa) were measured. The effects of different concentrations of glycyrrhetinic acid and verapamil, a P-glycoprotein inhibitor, Effect on intestinal absorption of glycyrrhetinic acid. Results There was no significant difference in Peff, Ka and Fa between 10 and 20μg / m L glycyrrhetinic acid perfusate in ileum. After adding 100μmol / L verapamil, Peff and Fa of 10μg / m L glycyrrhetinic acid increased , Indicating glycyrrhetinic acid may be P-gp substrate; compatibility of two ingredients, glycyrrhetinic acid intestinal absorption of baicalin the most obvious, the glycyrrhetinic acid Peff value from (4.05 ± 0.78) × 10-5 cm / s to (2.18 ± 0.63) × 10-5 cm / s, which can reduce the infiltration of glycyrrhetinic acid. Puerarin, berberine had no significant effect on the infiltration of glycyrrhetinic acid. The results of three kinds of ingredients compatibility show that after compatibility of glycyrrhetinic acid with puerarin and berberine, the osmotic coefficient does not change. The osmotic coefficient of glycyrrhetinic acid and puerarin and baicalin changed after compatibility, but the change was not obvious. Permeation decreased with the combination of baicalin and baicalin, and the Peff value decreased from (4.05 ± 0.78) × 10-5 cm / s to (1.35 ± 0.69) × 10-5 cm / s. The effect of baicalin on licorice Sour intestinal absorption of the most obvious. Conclusion Glycyrrhetinic acid can be well absorbed in the ileum of rats. A certain range of drug concentration has no significant effect on the Peff and Ka of glycyrrhetinic acid. The absorption mechanism of the glycyrrhetinic acid is passive diffusion. The glycyrrhetinic acid is P- gp substrate, and there is the phenomenon of transporter saturation; baicalin on the absorption of glycyrrhetinic acid significantly, probably through the induction of P-gp expression, increased glycyrrhetinic acid from the cell to the cell’s efflux, decreased Glycyrrhetinic acid infiltration, affecting its absorption.