摘要
目的:探讨P-糖蛋白(P-gp)的药泵作用对小肠吸收诺氟沙星皈影响。方法:运用十二烷基硫酸钠聚丙烯酰胺凝胶蛋白电泳(SDS-PAGE)法和体外外翻小肠囊吸收实验研究大鼠小肠P-gp的药泵作用对诺氟沙星吸收的影响程度。结果:在SDS-PAGE实验中,诺氟沙星、维拉帕米、普罗帕酮作为异生化合物能够诱导P-gp的表达,与空白对照组(0.9％氯化钠溶液组,A组)相比,其他各组P_gp的表达量都有明显的增加,其中诺氟沙星(B组)、诺氟沙星加维拉帕米(E组)和诺氟沙星加普罗帕酮(F组)有显著增加(P<0.05)。在体外外翻小肠囊吸收实验中,加入逆转剂维拉帕米和普罗帕酮能够显著提高浆膜侧诺氟沙星的浓度(P<0.05)。结论:大鼠小肠的P-gp药泵作用能够减少诺氟沙星的吸收,体外合并应用逆转剂可以改善诺氟沙星的小肠吸收;长期给予药物逆转剂能够诱导P-gp的表达,诺氟沙星的小肠吸收与P-gp相关。
Objective: To study the influence of intestine P-glycoprotein drug pumping in rats on norfloxacin absorption. Method: Drug pumping effect of intestine P-glycoprotein in rats on norfloxacin absorption was studied by SDS-PAGE and everted sac absorption method in vitro. Results: In SDS-PAGE experiment, norfloxacin, verapamil, and propafenone as xenobiotics induced P-glycoprotein expression. P-glycoprotein expressions in experimental groups, especially in group B (norfloxacin), group E (norfloxacin with verapamil), and group F (norfloxacin with propafenone), were significantly increased than in the control group (P<0.05). In everted sac experiment, co-administration of verapamil and propafenone as reverser could significantly increase norfloxacin concentration in the serous side (P<0.05). Conclusion: Intestine P-glycoprotein in rats can decrease norfloxacin absorption by drug-efflux pump, and co-administration of reversers can improve intestinal absorption of norfloxacin in vitro. P-glycoprotein expression can be raised by long term administration of norfloxacin, verapamil or propafenone. Intestinal absorption of norfloxacin is related with intestine P-glycoprotein.
出处
《医药导报》
CAS
2004年第5期283-287,共5页
Herald of Medicine
基金
国家自然科学基金(基金编号:30070899)
