基于原位单向肠灌流模型研究没食子酸的肠吸收特性

目的考察没食子酸的肠道吸收特性,为提高鞣质类成分生物利用度提供理论依据。方法采用大鼠在体肠单向灌流模型、建立HPLC测定没食子酸的方法,并计算没食子酸在各肠段的吸收速率常数(Ka)及有效表观渗透率系数(Peff);分别研究吸收部位、药物浓度、时间、pH值、P-糖蛋白(P-gp)和多药耐药相关蛋白-2(MRP2)抑制剂对没食子酸吸收的影响。结果没食子酸在不同肠段的Ka顺序为空肠>十二指肠>回肠≈结肠;随着药物浓度的升高,没食子酸的吸收差异无显著性;酸性环境(pH 5.5)有利于没食子酸的吸收;加入P-gp和MRP2抑制剂后,没食子酸的吸收与不加P-gp和MRP2抑制剂比较差异有显著性(P<0.05)。结论没食子酸在大鼠肠道内有较好的吸收,在空肠中吸收最好。初步判断其吸收机制为被动扩散。没食子酸的吸收受P-gp和MRP2的外排影响,可能为P-gp和MRP2底物。

Study on rat small intestinal absorption characteristics of gallic acid based on single-pass perfusion model

Aim To investigate the absorption characteristics of gallic acid in the intestine,and to provide a theoretical basis for improving the bioavailability of tannins.Methods Single-pass intestinal perfusion(SPIP)model was used for rat in situ and HPLC to determine the concentration of gallic acid.The absorption rate constant Ka and effective apparent permeability coefficient Peff of gallic acid in each intestinal segment were calculated.The effects of different intestinal segments,drug concentrations,pH value,P-glycoprotein(P-gp),and multidrug resistance protein2(MRP2)on intestinal absorption were assessed.Results The absorption rate constant(Ka)of gallic acid decreased following the sequence of jejunum>duodenum>ileum≈colon.With the increase of drug concentration,there was no significant difference in the absorption of gallic acid.The acidic environment(pH 5.5)was conducive to the absorption of gallic acid.After the addition of P-gp and MRP2 inhibitors,the absorption of gallic acid was significantly different from that without P-gp and MRP2 inhibitors(P<0.05).Conclusions Gallic acid can be well absorbed in the intestine of rats,and is best absorbed in jejunum.The absorption mechanism is determined to be passive diffusion.The gallic acid absorption process is affected by the efflux of P-gp and MRP2,which may be the P-gp and MRP2 substrates.