中文摘要：

目的：研究远志水解产物苷类和酮类成分在大鼠不同肠段的吸收特性及其机制,并考察P-糖蛋白（Pgp）和多药耐药相关蛋白2（MRP2）对细叶远志皂苷（TF）和远志酮Ⅲ（PT）肠吸收的影响。方法：采用在体单向肠灌流模型,用重量法校正灌流液体积,通过HPLC-DAD法测定肠灌流液中TF和PT的质量浓度,并考察吸收部位、助溶剂及抑制剂对受试药物吸收的影响。计算TF和PT的吸收速率常数（Ka）和表观吸收系数（Papp）。结果：当吐温-80作溶剂时,TF在结肠的Ka、Papp值均显著高于其他肠段（P〈0.05或P〈0.01）;PT的Ka呈结肠〉十二指肠〉空肠〉回肠趋势,但各肠段无显著性差异（P〉0.05）。当十二烷基硫酸钠（SDS）作溶剂时,仅结肠TF的Papp值显著高于十二指肠段（P〈0.05）。以SDS作助溶剂,与空白对照组比较,加入P-gp抑制剂盐酸维拉帕米（VH）0.1 mmol/L能显著增加TF的Ka值（P〈0.05）;VH各浓度均能显著增加PT的Ka值（P〈0.05,P〈0.01）。加入MRP2抑制剂吲哚美辛（IT）0.02、0.04 mmol/L能显著增加TF的Papp值（P〈0.05,P〈0.01）;IT 0.04、0.08 mmol/L能显著增大PT的Ka值（P〈0.05,P〈0.01）。结论：远志水解产物TF主要在结肠吸收,而PT则主要在十二指肠吸收。TF的肠吸收受P-gp外排影响,但不受MRP2外排影响,TF可能是P-gp的底物。PT的肠吸收均受P-gp与MRP2外排影响,PT可能是P-gp和MRP2的底物。若含细叶远志皂苷和远志酮Ⅲ类制剂与P-gp和/或MRP2抑制剂联用,可能会促进其吸收。

英文摘要：

Objective： To evaluate the absorption feature and mechanism of tenuifolin（ TF） and polygalaxanthone Ⅲ（ PT） in different intestinal parts of rats and the impact of MRP2 and P-glycoprotein（ P-gp） on it. Methods： In situ unidirectional perfusion was used to detect the concentration of TF and PT through HPLC-DAD with gravimetric method. Furthermore,impact of different parts,cosolvents and inhibitors to TF and PT was also explored with data of Kaand Papp. Results： Tween as cosolvent,Kaand Pappof TF was significantly higher in colon than in other intestinal parts（ P〈0. 05 or P〈0. 01）. Whereas,Kaof PT was in sequence of colon,duodenum,jejunum,ileum,but with no significant difference among them（ P〉0. 05）. SDS as cosolvent,Pappof TF was higher in colon than in duodenum（ P〈0. 05）. Kaof TF was significantly higher compared with control when added with VH,an inhibitor of P-gp（ P〈0. 05）. In addition,Pappof PT in different concentration of VH increased（ P〈0. 05,P〈0. 01）. Pappof TF significantly increased with IT at the concentration of 0. 02 and 0. 04 mmol / L,an inhibitor of MRP2（ P〈0. 05,P〈0. 01）. Meanwhile,Kaof PT,with IT at the concentration of 0. 04 and 0. 08 mmol / L,was significantly higher（ P〈0. 05,P〈0. 01）. Conclusion： TF is mainly absorbed in colon,whereas PT is in duodenum. P-gp but not MRP2 influences the intestinal absorption of TF,indicating TF as substrate of P-gp. However,both of P-gp and MRP2 impact the absorption of PT,illustrating PT as substrate of P-gp and MRP2. It also indicates that inhibitors of P-gp and / or MRP2 in combined application may improve the absorption of PT and TF.