甘草与芫花对P-糖蛋白底物罗丹明123经空肠黏膜透过性的影响  

Effect of Glycyrrhiza inflata and Daphne genkwa on permeabilities of rhodamine 123,a P-glycoprotein substrate across rat jejunum membranes in vitro

作　　者：黄蓓蓓[1] 李国锋[1] 任非[1] 唐中昆[2] 马华飞[1] 孙亚彬[1] 陈莉婧[1] 杨凌[1] 

机构地区：[1]南方医科大学南方医院药学部,广东广州510515 [2]南方医科大学药学院药物化学系,广东广州510515

出　　处：《中国中药杂志》2008年第21期2521-2526,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(C03050205);广东省科技计划项目(2005B30101007);2006年笹川医学奖学金同学会科研启动基金(101号)

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、芫花及其合用影响药物经胃肠道渗透的可能作用机制。方法:将25只Wistar大鼠分为5组,分别给大鼠口服甘草液、芫花液、甘草芫花合煎液、合并液以及生理盐水,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)经空肠黏膜透过性的影响,用荧光分光光度法测定R123和CF的浓度,并分析各组表观渗透系数(Papp)差异。结果:4种药液均具有增加R123经吸收方向的透过性,与生理盐水组比较,P<0.05,且芫花液、合煎液以及合并液还可减少分泌方向的透过(P<0.05,与生理盐水组比较),甘草对分泌方向透过影响无统计学意义。甘草对CF透过无影响,而其他3组药液则可减少CF吸收和分泌方向的透过性。结论:甘草和芫花对P-gp均有抑制作用,但后者作用较强。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,这可能是两者配伍产生毒性的机制之一。Objective： To investigate the modulation of Glycyrrhiza inflata and Daphne genkwa on the permeability characteristics of rhodamine 123 （R123）, one P-glycoprotein （P-gp） substrate, across the jejunum membranes. And then approach the possible permeability mechanism of the drugs after co-administration of G. inflata and D. genkwa in gastrointestinal tract. Method： The permeability of R123 or fluorescein sodium （CF） via Wistar rat jejunum membranes was evaluated by in vitro diffusion chamber system after oral administration of four different decoctions and 0.9% sodium chloride （20 mL · kg^-1 ） for 1 week. And the concentration of R123 or CF was determined by the fluorospectrophotometry. The apparent permeability coefficient （Papp） was calculated by the equation P,pp = d0/d1× （1/A · Co ）, where Papp was expressed in cm/s, dQ/dr was the slope of the linear portion of the permeation curves, Awas the diffusion area, and Co was the initial concentration of rebamipide in the donor side, and then compare their differences were compared with control group. Result： After oral administration of G. inflata decoction, D. genkwa decoction and decoction of the combination of the previous decoctions, the absorptive directed transport of R123 was significantly increased （ P 〈0.05, compared with control group）. On the other hand, D. genkwa could also decrease the permeability of secretory directed transport （Papp = 2. 98-0.59）, while no action of G. inflata was found on the secretory transport of R123 （Papp = 5.24 ± 3. 98 ） across the jejunum tissues, while Papp of control group was 4. 38 ＋ 1.18. Meanwhile, G. inflata had no effect on transport of CF across the jejunum tissues, though the other three groups could decrease the permeability of CF, as compared with control group. Conclusion： G. inflata may slightly in- hibit P-glycopretein function in the intestinal membrane, while D. genkwa may be a relatively strong inhibitor of P-gp. For another, some compositions in D. genkwa inhib

关 键 词：甘草 芫花 P-糖蛋白 扩散池 透过性 

分 类 号：R285.5[医药卫生—中药学]