环黄芪醇连续灌胃对大鼠肝脏P450酶活性的影响  

Effect of continuous oral cycloastragenol on the activity of cytochrome P450 enzymes in rats

作　　者：魏宝红[1] 叶静[1] 薛宝娟[1] 孙桂霞[1] 杨晓燕[1] 张玉杰[1] 

机构地区：[1]北京中医药大学中药学院,北京100102

出　　处：《中国新药杂志》2014年第4期476-479,共4页Chinese Journal of New Drugs

基　　金：北京中医药大学研究生自主课题(5320100604286)

摘　　要：目的:评价环黄芪醇连续灌胃诱导后对大鼠肝脏CYP450亚酶活性的影响。方法:大鼠连续7 d灌胃环黄芪醇溶液(40 mg·kg-1·d-1)诱导肝药酶后,采用cocktail探针底物与大鼠肝微粒体体外温孵法,通过HPLC同时测定5种探针药物美托洛尔、氨苯砜、非那西丁、氯唑沙宗和甲苯磺丁脲的代谢消除率,评价环黄芪醇对CYP2D6,CYP3A4,CPY2A1,CPY2E1和CPY2C9亚酶活性的影响。结果:环黄芪醇对CYP2E1亚酶显示出显著的诱导作用;对CYP3A4则呈显著的抑制作用,但对CYP2D6,CYP1A2和CYP2C9亚酶未表现出明显的影响;进一步测得其对CYP3A4的半数抑制浓度IC50为12.13μmol·L-1,抑制类型为竞争性抑制。结论:环黄芪醇对CYP3A4亚酶具有明显的抑制作用,对CYP2E1亚酶显示出显著的诱导作用。Objective： To determine the effect of cycloastragenol （CAG） on cytochrome P450 enzyme subtypes of rat liver microsomes. Methods： Rats were treated with CAG （40 mg-kg-1.d-1） for 7 days to induce hepatic microsomal enzyme. Cocktail probe substrates were incubated with liver microsomes in vitro. Then, the metabolic elimination percentages of the five probe substrates metoprolol, aminophenylsulfone, chlorzoxazone, phenacetin and tolbutamide were determined by HPLC. The effect of CAG on the enzymatic activity of rat liver microsomal CYP450s was evaluated. Results： Compared with the control, CAG obviously activated CYP2E1, and remarkably inhibited CYP3A4 CYP3A4 was 12.13 inhibit CYP3A4 and However, CAG did not significantly affect CYP2D6, CYP1A2 and CYP2C9. The ICs0 of umol. L-1, and inhibition type was competitive inhibition. Conclusion： CAG can remarkably activate CYP2E1.

关 键 词：环黄芪醇 肝脏CYP450亚酶 Cocktail探针法 抑制类型 大鼠 

分 类 号：R969.1[医药卫生—药理学]