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目的研究芫花水煎液对P-糖蛋白(P-gp)的底物罗丹明123(R123)在空肠内转运和吸收的影响,探讨芫花对肠黏膜P-gp的调控作用。方法大鼠分组制模,利用体外扩散池法(Ussing chamber)评价芫花对R123和荧光素钠(CF)经空肠黏膜透过性的影响;利用在体实验测定R123和CF在血浆中药物浓度的变化和各种药动学参数。结果一方面,0.5 g.mL-1的芫花水煎液降低了R123分泌方向的转运,同时提高了吸收方向的转运,而且对CF吸收和分泌方向的转运都有抑制作用;另一方面,在体实验芫花组R123的生物利用度和曲线下面积都显著大于对照组,CF则与对照组无明显差异。结论实验表明,芫花某些化学成分抑制P-gp,另一些成分可能使细胞之间紧密连接加强,引起旁细胞途径药物CF渗透的降低。因此芫花是肠黏膜P-gp的一种抑制剂,但是哪种化学成分发挥作用有待于进一步研究。
Objective To investigate the effect of Daphne genkwa on the transport and absorption of Rhodamine123 (P123), a substrate of P-glycoprotein (P-glycoprotein), in jejunum and to investigate the regulatory effect of Daphne genkwa on P-gp in intestinal mucosa. Methods Rats were divided into groups. Ussing chamber was used to evaluate the effects of Daphne genkwa on the permeability of R123 and sodium fluorescein (CF) through the jejunum mucosa. The plasma concentrations of R123 and CF Changes and various pharmacokinetic parameters. Results On the one hand, 0.5 g.mL-1 Daphne genkwa decoction decreased the translocation of R123 in the secretion direction, increased the transport in the absorption direction and inhibited the transport of CF in the absorption and secretion directions. On the other hand, The bioavailability and area under the curve of R123 in the Daphne genkwa group were all significantly higher than those in the control group, while there was no significant difference between CF and the control group. Conclusions Experiments show that some of the chemical components of Daphne genkwa inhibit P-gp, and other components may strengthen the tight junctions between cells, resulting in the reduction of CF permeation by paracellular pathway drugs. Therefore, Daphne genkwais is an inhibitor of intestinal mucosal P-gp, but which chemical composition to play a role needs further study.