甘草与芫花对P糖蛋白物罗丹明123经空肠粘膜透过性的影响.doc

甘草与芫花对P-糖蛋白底物罗丹明123经空肠粘膜透过性的影响 [摘要] 目的：观察甘草与芫花合用前后对P-糖蛋白(P-gp)的调控作用，探讨甘草、芫花及其合用液影响药物经胃肠道渗透的可能作用机理。方法：分别给大鼠口服甘草液、芫花液、甘草芫花合煎液以及合并液，1周后用体外扩散池法(Ussing chamber)评价各种药液对罗丹明123(R123)和荧光素钠(CF)经空肠粘膜透过性的影响，用荧光分光光度法测定R123和CF的浓度。结果：一方面四种药液均具有增加R123经吸收方向的透过性，且芫花液、合煎液以及合并液还可减少分泌方向的透过，甘草对分泌方向透过影响无统计学意义。另一方面，甘草对CF透过无影响，而其他三组药液则可减少CF吸收和分泌方向的透过性。结论：甘草可能对P-gp有一定的抑制作用，而芫花则是一种较强的P-gp抑制剂。一方面芫花某些化学成分抑制P-gp，而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。甘草与芫花合用后对P-gp抑制作用增强，可能是甘草对芫花有协同作用，使一些毒性成分吸收增加，这可能是是两者配伍产生毒性的机理之一。 [关键词] 甘草；芫花；P-糖蛋白；扩散池；透过性 Effect of Liquorice and Daphne genkwa on the permeabilities of rhodamine123,a P-Glycoprotein subatrate across the rat jejunum membranes in vitro [Abstract] Objective: To investigate the modulation of Liquorice and Daphne genkwa on the permeability characteristics of rhodamine 123(R123)，one p-glucoprotein substrate, across the jejunum membranes. And then approach the possible permeability mechanism of the drugs after co-administration of Liquorice and Daphne genkwa in gastrointestinal tract. Methods: Evaluated the permeability of R123 or fluorescein sodium (CF) via rat jejunum membranes by in vitro diffusion chamber system after oral administration of four different decoctions and 0.9% Sodium Chloride for 1 week .And the concentration of R123 or CF was determined by the fluorospectrophotometry. Result: After oral administration of Liquorice decoction ,Daphne genkwa decoction and decoction of the combination of the previous decoctions ,the absorptive directed transport of R123 was significantly increased. On the other hand, Daphne genkwa also can decrease the permeability of secretory directed transport, while no action of Liquorice was found on the secretory transport of R123 across the jejunum tissues. Meanwhile, Liquorice had no effect on transport of CF across the jejunum tissues, though the other three groups can decrease the permeability of CF, as compared with control group. Conclusion: Liquorice may slightly inhibit P-Glycoprotein (P-gp) function in th