基于大鼠在体单向肠灌流模型研究四制香附主成分肠吸收机制

目的:考察四制香附主成分(香附烯酮、α-香附酮)肠吸收机制。方法:采用大鼠在体单向肠灌流模型,考察香附烯酮、α-香附酮、四制香附石油醚部位模拟体系(单体混合物)及四制香附石油醚部位中香附烯酮、α-香附酮在大鼠各肠段的吸收情况,研究乙二胺四乙酸(EDTA)及盐酸维拉帕米对吸收的影响。结果:香附烯酮与α-香附酮在小肠各段均有吸收,香附烯酮在回肠段吸收最好,α-香附酮在空肠段吸收最好;香附烯酮与α-香附酮在一定浓度范围内,肠吸收参数Ka与Peff无显著性差异;加入EDTA及盐酸维拉帕米后,肠吸收参数Ka与Peff无显著性差异;与单体比较,单体混合物和四制香附石油醚部位中的香附烯酮、α-香附酮吸收参数Ka和Peff差异均有统计学意义(P<0.05)。结论:香附烯酮及α-香附酮的肠吸收机制可能为被动扩散,细胞旁路转运及P-gp不参与其转运;香附烯酮与α-香附酮的肠吸收存在协同作用,石油醚部位中其他成分可促进香附烯酮、α-香附酮的肠吸收。

Intestinal absorption mechanism of Cyperi Rhizoma with Jianchangbang by single pass intestinal perfusion model in rats

Objective: To investigate the absorption mechanisms of major components of Cyperi Rhizoma. Methods: In situ single pass intestinal perfusion model was used, intestinal absorption of pure cyperotundone, pure α-cyperone, simulated system of the petroleum ether part of Cyperi Rhizoma, the petroleum ether part of Cyperi Rhizoma and α-cyperone in perfusion solution of different intestinal segments were determined by HPLC, the effects of Ethylene Diamine Tetraacetic Acid(EDTA) and Verapami on their absorption were investigated. Results: Cyperotundone and α-cyperone were absorbed in the whole of small intestine, cyperotundone was the best in the ileum and α-cyperone was the best in the jejunum. In a certain concentration range of cyperotundone and α-cyperone, there were no significant differences in intestinal absorption parameters between Ka and Peff. There were no significant differences in intestinal absorption parameters between Ka and Peff after the addition of cell bypass transport inhibitor EDTA and P-gp inhibitor verapamil. Compared with the monomers, there were significant differences in absorption parameters Ka and Peff of cyperotundone and α-cyperone between the simulated system and the petroleum ether part of Cyperi Rhizoma(P<0.05). Conclusion: The intestinal absorption mechanisms of cyperotundone and α-cyperone were mainly the passive diffusion, and cell bypass transport and P-gp were not involved in their transport. There was a synergistic effect between cyperenone and α-cyperenone in intestinal absorption. Other components in the petroleum ether part could promote the intestinal absorption of Cyperus and α-Cyperus.