摘要
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 examine the effect of Daphne genkwa on the intestinal transport and absorption of rhodamine 123（R123）,a P-glycoprotein（P-gp） substrate,across the jejunum membranes,and to investigate the modulation of Daphne genkwa on the function of the intestinal P-gp.METHODS The permeability of R123 or fluorescein sodium（CF） via Wistar rat jejunum membranes was evaluated by in vitro diffusion chamber system.Rat plasma concentrations were measured and pharmacokinetic parameters of R123 and CF were analyzed by an in situ experiment after oral administration Daphne genkwa decoctions and 0.9% sodium chloride.RESULTS 0.5 g·mL-1 Daphne genkwa decoctions increased the absorptive transport of R123 and decreased the secretory transport in vitro.However,it also decreased the permeability of CF.In the in situ absorption,Daphne genkwa（0.5 g·mL-1） significantly enhanced the intestinal absorption of R123 in rats,and showed no effect on the absorption of CF.CONCLUSION Some compositions in Daphne genkwa which inhibit P-gp function,and some others strengthen the tight junction among cells in the intestinal membrane to decrease permeability of CF.Therefore,Daphne genkwa may be a relatively strong inhibitor of P-gp.It is necessary to investigate the composition in Daphne genkwa which inhibit P-gp in the future.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2010年第1期23-27,共5页
Chinese Pharmaceutical Journal
基金
国家自然科学基金资助课题(C03050205)
广东省科技计划项目资助课题(2005B30101007)
2006年笹川医学奖学金同学会科研启动基金(101号)
关键词
芫花
罗丹明123
P-糖蛋白
肠吸收
体外扩散池
Daphne genkwa rhodamine 123 P-glycoprotein intestinal absorption Ussing chamber
