白头翁皂苷D在大鼠肠道的吸收行为研究

目的 考察白头翁皂苷D在大鼠肠道的吸收特性。方法 采用大鼠在体单向肠灌流模型考察白头翁皂苷D在大鼠肠道的吸收情况，HPLC法测定肠灌流液中的白头翁皂苷D，以白头翁皂苷D的吸收速率常数（K_a）和表观渗透系数（P_app）为指标，考察吸收部位、药物浓度、pH值和P-糖蛋白（P-gp）抑制剂对白头翁皂苷D吸收的影响。结果 白头翁皂苷D灌流液在各肠段的K_a和P_app值为结肠＞回肠＞空肠＞十二指肠，且各肠段之间存在显著差异（P＜0.05）；随着pH值不断增加，K_a和P_app值也随之增加，且K_a和P_app均存在显著差异（P＜0.05）；不同质量浓度（0.30、0.15、0.08 mg/mL）的灌流液在结肠的吸收无显著差异；灌流液中含P-gp抑制剂与不含P-gp抑制剂的白头翁皂苷D的肠吸收存在显著差异（P＜0.05）。结论 白头翁皂苷D在大鼠各肠段均能较好地被吸收，吸收窗主要在结肠；一定范围内的药物质量浓度对白头翁皂苷D的K_a和P_app无明显影响，初步确定其吸收机制为被动扩散；白头翁皂苷D是P-gp的底物，且存在转运蛋白饱和现象。

Study on in situ intestinal absorption of Pulsatilla saponin D in rats

Objective To investigate the intestinal absorption characteristics of Pulsatilla saponin D in rats. Methods In situ single-pass intestinal perfusion model was used to inspect the absorption of Pulsatilla saponin D in the intestinal tract of rats. HPLC was used to determine the concentration of Pulsatilla saponin D in intestinal perfusion fluid samples. Absorption rate constant (K_a) and apparent permeability coefficient (P_app) were used as indexes to investigate the effects of absorption sites, drug concentration, different pH values, and P-glycoprotein (P-gp) inhibitor on Pulsatilla saponin D absorption. Results There was the significant difference (P < 0.05) of intestinal perfusion fluid samples in each intestinal segment and the order of the K_a and P_app values of Pulsatilla saponin D in each intestinal segment was colon > ileum > jejunum > duodenum. With the pH value increasing, the K_a and P_app values also increased and both of them had significant differences (P < 0.05). The colon absorption of perfusion fluid at different concentration (0.30, 0.15, and 0.08 mg/mL) had no significant difference (P > 0.05); There was significant difference (P < 0.05) in K_a and P_app values with and without P-gp inhibitor. Conclusion Pulsatilla saponin D could be well absorbed in whole intestinal segments of rats, and the best intestinal absorption site is colon; The drug concentration in a certain range has no effect on K_a and P_app values, which preliminarily comfirms that the obsorption mechanism of Pulsatilla saponin D could be passive diffusion; Pulsatilla saponin D may be a substrate of P-gp and possess the saturation phenomenon of transporters.