应用Ussing Chamber技术评价甘草与海藻的配伍对大鼠肠黏膜P-gp的影响  

Modulation on the P-glycoprotein in the Jejunum by Combined Use of Glycyrrhiza inflata and Sargassum in Vitro

作　　者：孙亚彬[1] 李国锋[1] 刘思佳[1] 陈英[1] 唐中昆[2] 赵博欣[1] 

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

出　　处：《中国药学杂志》2010年第8期585-589,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(C03050205);笹川医学奖学金同学会科研启动基金(101号)

摘　　要：目的评价甘草海藻配伍对大鼠肠黏膜P-糖蛋白(P-gp)的影响。方法通过对大鼠口服甘草煎液、海藻煎液、甘草海藻合煎液及其合并液、生理盐水1周后,使用Ussing Chamber技术,评价罗丹明123(R123)和荧光素钠(CF)经大鼠空肠黏膜的经时吸收方向和分泌方向的透过量和表观渗透系数。R123和CF在接受室的浓度用荧光分光光度计检测。结果4种药液均具有增加R123经吸收方向透过性的趋势,但仅海藻使R123吸收方向的透过性显著增加(P<0.05,与生理盐水组比较)。同时,海藻也使R123分泌方向的透过性显著增加(P<0.01,与生理盐水组比较)。但海藻与甘草合用后,合煎组与合并组使R123分泌方向的透过性显著减少(P<0.01,与生理盐水组比较);另外,海藻与甘草的单煎液、合煎液、合并液对CF经空肠黏膜转运的吸收方向及分泌方向的透过性与生理盐水比较,均无显著性差异。结论海藻可能不对P-gp起抑制作用。海藻中的某些成分可能改变了细胞膜通透性,从而增加了跨膜转运药物R123吸收分泌双方向的渗透,但对细胞间的药物转运影响不大。海藻和甘草合用后对肠黏膜P-gp起到了一定抑制作用,引起海藻和甘草中P-gp底物的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 on the P-glycoprotein in the jejunum by combined use of Glycyrrhiza inflata and Sargassum with Ussing Chamber in vitro.METHODS The permeability of rhodamine123（R123） or fluorescein sodium（CF） via Wistar rat jejunum membranes was evaluated by in vitro Ussing Chamber after oral administration of four different decoctions of Glycyrrhiza inflata and Sargassum and 0.9% sodium chloride for 1 week.And the concentration of R123 or CF were determined by the fluorospectrophotometry in the receiving solution.RESULTS After oral administration of Glycyrrhiza inflata decoction,Sargassum decoction and decoction of the combination of the previous two decoctions,the absorptive directed permeability of R123 was increased,while only in Sargassum group,the permeability of R123 was increased with significant difference（P〈0.05）,compared with the control group.Sargassum also increased significantly the secretory transport of R123,compared with control group（P〈0.01）.However,the secretory transport of R123 by combined administration of the two decoctions was decreased（P〈0.01）,as compared with the control group.All the decoctions had no effect on transport of CF across the jejunum tissues.CONCLUSION Sargassum may not be an inhibitor of P-glycoprotein function in the intestinal membrane.Some compositions in Sargassum may strengthen the membrane＇s permeability to increase the bilateral transport of R123.There was no effect of Sargassum on the bilateral transport of CF.Considering the inhibitory action on P-gp enhanced by combination of Glycyrrhiza inflata and Sargassum,it may be one of the mechanisms of toxicity once co-administration of Glycyrrhiza inflata and Sargassum.

关 键 词：海藻 甘草 Ussing Chamber技术 P-糖蛋白 

分 类 号：R965[医药卫生—药理学]