多成分环境下甘草次酸肠吸收行为的研究  

Research on intestinal permeability of glycyrrhetinic acid in multicomponent environment

作　　者：董月柳 李雪莲[1] 陈江鹏[1] 孙慧娟[1] 潘孟[1] 王子禹 董玲[1] 

机构地区：[1]北京中医药大学,北京100102

出　　处：《中草药》2017年第16期3396-3400,共5页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81473362)

摘　　要：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 characteristics of intestinal absorption of glycyrrhetinic acid in rats in the multicomponent environment. Methods The effect of multicomponent environment on intestinal absorption of glycyrrhetinic acid was investigated in rat model of in situ single-pass intestinal perfusion, HPLC was used to determine the concentration of glycyrrhetinic acid in intestinal perfusion fluid samples, the effective permeability coefficient（Peff）, absorption rate constant（Ka）, and absorption fraction（Fa） of glycyrrhetinic acid in rats ileum were calculated, the effects of glycyrrhetinic acid with different mass concentration and P-glycoprotein（P-gp） inhibitor verapamil, as well as the compatibility of different components on intestinal absorption of glycyrrhetinic acid were examined,. Results The Peff, Ka, and Fa values of glycyrrhetinic acid perfusion liquid（10 and 20 μg/m L） in the ileum segment had no significant difference. Added with 100 μmol/L verapamil, Peff, and Fa values of 10 μg/m L glycyrrhetinic acid increased, which illustrated that the glycyrrhetinic acid might be the substrate of P-gp; In two components compatibility, the effect of baicalin on absorption of glycyrrhetinic acid was the most obvious, Peff value of glycyrrhetinic acid was from（4.05 ± 0.78） × 10^-5 cm/s to（2.18 ± 0.63） × 10^-5 cm/s, and the penetration of glycyrrhetinic acid was reduced. The puerarin consociation baicalin and berberine had no obvious effect on permeability of glycyrrhetinic acid. In the three components compatibility condition, the experimental results showed that after glycyrrhetinic acid combined with puerarin and berberine, the permeability coefficient did not change, while the permeability coefficient changed, but not obviously, glycyrrhetinic acid combined with baicalin and berberine had lower permeability, Peff values were from（4.05 ± 0.78） × 10^-5 cm/s down to（1.35 ± 0.69） × 10^-5 cm/s, and the effects of baicalin on glycyrrhetinic acid was evident. Conclus

关 键 词：甘草次酸 多成分环境 在体单向肠灌流 P-糖蛋白 肠渗透 

分 类 号：R285.62[医药卫生—中药学]