荆芥内酯大鼠在体肠吸收动力学研究

Study on the Intestinal Absorption Kinetics of Schizonepetin in Rats

目的研究荆芥内酯在大鼠小肠中的吸收动力学特征。方法建立大鼠在体肠循环模型,采用酚红标记法校正循环液体积,HPLC测定不同时刻循环液中荆芥内酯的含量。结果不同质量浓度(1.84、3.68、7.36μg.mL-1)荆芥内酯的吸收速率常数Ka分别为(0.202 8±0.007 0)、(0.158 9±0.011 4)、(0.134 2±0.012 2)h-1,且各组之间均有显著性差异(P<0.05);质量浓度为3.68μg.mL-1的荆芥内酯在大鼠十二指肠、空肠、回肠的吸收速率常数Ka分别为(0.023 8±0.000 6)、(0.012 5±0.000 5)、(0.016 5±0.000 8)h-1,各组之间均有显著性差异(P<0.05)。结扎胆管与否以及肠道菌群的破坏,对荆芥内酯的肠吸收影响不大。加入P-gp抑制剂组与对照组比较,其Ka值之间存在显著性差异(P<0.05)。结论荆芥内酯在大鼠肠道的吸收呈一级动力学过程,吸收机制为主动转运;在大鼠各肠段均有吸收,其中十二指肠为其最佳吸收部位。

OBJECTIVE To investigate the absorption kinetics; of schizonepetin in intestines of rats. METHODS In situ recirculation model was established in rats. The volume of recirculation fluid was adjusted by phenol red. The contents of schizonepetin at different point time were detected by HPLC. RESULTS The absorption rate constant （Ka） of schizonepetin at low, middle and high concentrations （ 1.84, 3.68 and 7. 36 μg . mL-1 ） were （0. 202 8 ±0. 007 0）, （0. 158 9 ±0. 011 4） and （0. 134 2 ±0. 012 2） h-1, respectively, showing significant differences （P 〈 0. 05）. The Ka of schizonepetin at concentration of 3.68 μg . mL- 1 at duodenum, jejunum and ileum were （0. 023 8 ±0. 000 6）, （0. 012 5 ±0. 000 5） and （0. 016 5 ±0. 000 8） h 1, respectively （P 〈0. 05）. Bile duct ligation and intestinal flora had little influence on the intestinal absorption of schizonepetin. The Ka of P-gp inhibitor group had sig- nificant difference with that of the control group （P 〈 0.05）. CONCLUSION The absorption of schizonepetin follows first-order process with active diffusion mechanism. Schizonepetin can be absorbed at all intestinal segments, and duodenum is the best absorption site.