炒白芍提取物在大鼠肠外翻囊实验中的吸收及与P 炒白芍提取物在大鼠肠外翻囊实验中的吸收及与P gp相互作用研究

目的：研究炒白芍提取物中芍药苷(Pae)在大鼠不同肠段的肠外翻囊模型中的吸收动力学特征及其与Pgp的相互作用。方法：采用大鼠肠外翻囊模型，以Pae为炒白芍提取物中代表成分，用HPLC对其进行检测，计算Pae的肠吸收动力学参数，分析Pae的肠吸收特征。结果：炒白芍提取物不同浓度时Pae在不同肠段的吸收均为线性吸收，其回归相关系数的平方(R2)均>0.9以上，符合零级吸收；其Ka随给药剂量的增加而增加，说明其为被动吸收。Pae在不同肠段吸收总趋势为空肠>回肠>结肠。炒白芍提取物与维拉帕米(Ver)合用时，Pae在回肠中吸收显著增加(P<0.05)；口服炒白芍提取物后，在回肠段对Rho 123的外排量增加(P＜0.01)。结论：Pae在肠道中吸收为零级吸收，吸收机制为被动吸收。Pae可能为Pgp底物，炒白芍提取物能诱导肠道中Pgp的表达。

Absorption of extractive Radix Paeoniae Alba in rat everted gut sacs and its interaction with P glycoprotein

Objective: To research the intestinal absorption characteristics of paeoniflorin in extractive Radix Paeoniae Alba in the different intestinal segment, and the interaction with P glycoprotein.  Method: Paeoniflorin, a representative component in extractive Radix Paeoniae Alba, on the intestinal absorption was studied in vitro using everted gut sacs model and detected by HPLC method. The absorption characteristics was evaluated by the absorption parameter.  Result: The absorption of paeoniflorin was linearity at different intestine segment and dose, and the square of regrees correlation coefficient exceed 0.9 (R2>0.9), which consistent with zero order rate process. The Kα of paeoniflorin showed a dose dependent increase along with the raised dose of extractive Radix Paeoniae Alba, indicated it was a mechanism of passive absorption. The absorption rate was jejunum>ileum>colon. Verapamil (100 μmol·L-1), a inhibitor of the P glycoprotein, can remarkable increase the absorption of the paeoniflorin in ileum (P<0.05). After administer the extractive Radix Paeoniae Alba for 5 days, the extraction of Rho123 is significantly increase in ileum (P<0.01).  Conclusion: The intestinal absorption of paeoniflorin is zero order rate process and passive absorption. Paeoniflorin is a substrate of P glycoprotein, and extractive Radix Paeoniae Alba could induce the expression of the P glycoprotein.