黄连黄芩配伍对大鼠肠黏膜P-gp活性的影响

目的:评价连续ig黄连、黄芩提取液及其黄连-黄芩合煎液对大鼠肠黏膜上P-糖蛋白( P-glycoprotein,P-gp)活性的影响,探讨黄连-黄芩药对配伍的机制.方法:将大鼠随机分为5组.连续ig黄连、黄芩提取液及其合煎液1周诱导后,采用非翻转肠囊和翻转肠囊实验,以累计渗透率和表观渗透系数(Papp)为考察指标,体外评价P-gp底物罗丹明123( rhodamine123,R123)和非P-gp底物荧光素钠(fluorescein sodium,Fs)经大鼠空肠黏膜吸收方向(M-S)和分泌方向(S-M)的转运变化.结果:黄连提取液能减少R123经空肠M-S方向的转运(P＜0.05),对S-M方向转运没有显著影响.黄芩及其黄连-黄芩合煎液均能不同程度的增加R123经空肠M-S方向的转运,同时可不同程度的降低S-M方向的转运.在评价各组药液对旁细胞转运药物FS影响的实验中,黄连、黄芩和黄连-黄芩合煎液(2∶1)组在M-S和S-M双活性方向对FS的透过性均无显著影响,而黄连-黄芩合煎液(1∶1)组可同时降低双方向的透过性.各组的泵出比较生理盐水组无显著差异.结论:黄连提取液连续ig可增加大鼠肠黏膜上P-gp的活性,而黄芩对P-gp的活性具有一定的抑制作用,合煎液与黄芩相似,但抑制作用更强.与生理盐水组相比,三者抑制作用强弱顺序为1∶1合煎组最强,2∶1合煎组次之,黄芩组最弱.

Induction of P-glycoprotein in Rat Jejunum by Combined Use of Coptis-scute Herb

Objective: To investigate the effect of Coptis-scute herb and combined ( 2 :1,1 :1 ) use on the P-glycoprotein function in rat jejunum. Method: The rats were randomly divided into five groups. Rhodamine 123(R123) and fluorescein sodium (FS), a P-gp substrate and a non-P-gp substrate model drug were taken as investigating indicator. After oral administration of four different decoctions of Coptis-scute herb and its combination (2 :1,1 :1) for successive 7 days, the cumulative permeability percentage and the apparent permeability coefficient (Papp) of R123 or FS were evaluated by applying a rat everted gut sac as well as a non everted gut sac method. Result: The absorptive directed permeability (mucosa to serosa, M-S) of R123 can be increased after oral administration of Coptis decoction, and on the other hand, the secretory directed transport (serosa to mucosa, S-M) be decreased, but there is no significant effect. The other three groups can increase M-S of R123 as well as reduce S-M, but there is no significant difference on the S-M after oral administration of Scute decoction. In parietal cells transport of FS, no significant effect can be found in Coptis-scute herb and its combination 2 : 1 group on two direction transport but decreased effect can be found in combination1 : 1 group. Comparing with the efflux ratios (ER) of physiological saline, there are no significant differences on the four groups. Conclusion: Coptis could increase P-gp activity,and Scute may have opposite effect. The rest of the two groups have stronger inhibition than Scute. 1 : 1 group was the strongest one, followed by 2 : 1, the weakest was the Scute group.