黄芪颗粒和黄芪注射液对CYP1A2、CYP2D、CYP2C亚酶活性影响的实验研究

目的通过体内和体外实验研究黄芪颗粒和黄芪注射液对CYP1A2、CYP2D、CYP2C亚酶的活性影响。方法建立体外"cocktail"反应体系,利用LC/MS/MS法测定酶代谢产物,计算黄芪颗粒和黄芪注射液对CYP1A2、CYP2D6、CYP2C9和CYP2C19亚酶活性的影响;大鼠随机分为对照组和实验组,不同浓度黄芪颗粒和黄芪注射液连续灌胃10 d,制备肝微粒体并进行"cocktail"反应,评价两种药物体内对大鼠CYP1A2、CYP2D1、CYP2C6和CYP2C11亚酶活性影响。结果在体外"cocktail"实验中,黄芪颗粒和黄芪注射液明显地抑制了CYP2D6、CYP2C19和CYP1A2亚酶活性,而二者对于CYP2C9亚酶活性无影响。在大鼠灌胃给药实验中,黄芪颗粒在剂量32、160和800 mg.kg-1.d-1提高CYP1A2亚酶活性2.13、3.23和2.20倍,黄芪注射液在剂量0.16、0.8、4 g.kg-1.d-1提高CYP1A2亚酶活性1.65、2.26和2.89倍,而二者均未诱导CYP2D1、CYP2C6和CYP2C11亚酶活性增加。结论黄芪颗粒和黄芪注射液对CYP2D6、CYP2C19活性有抑制作用,对大鼠CYP1A2活性有诱导作用。

Experimental study on effect of Astragalus granules and Astragalus injection on enzymatic activities of CYP1A2, CYP2D and CYP2C

Aim To study the effects of Astragalus granules and Astragalus injection on the enzymatic activities of CYP1A2,CYP2D and CYP2C through the experimental researches in vivo and in vitro.Methods A"cocktail" vitro reaction system was established.Metabolins of enzymes were detected by the methods of LC/MS/MS.The effect of Astragalus granules and Astragalus injection on the enzymatic activities of CYP1A2,CYP2D6,CYP2C9 and CYP2C19 isoforms were calculated.Rats were randomly divided into the control groups and the experimental groups,each group got gavage administrations of different concentrations of Astragalus granules and Astragalus injection for 10 days.Then the liver microsomes were prepared to proceed the experiment of cocktail to assess the effects in rats of two kinds of drugs on the enzymatic activities of CYP1A2,CYP2D1,CYP2C6 and CYP2C11 isoforms in vivo.Results Enzymatic activities of CYP2D6,CYP2C19 and CYP1A2 isoforms were suppressed significantly by Astragalus granules and Astragalus injection in vitro experiments of cocktail.But they had no effect on the CYP2C9 isoform.In the experiments of gavage administration,enzymatic activity of CYP1A2 isoform increased significantly by 2.13,3.23 and 2.20 times when the doses of Astragalus granules were 32,160 and 800 mg·kg-1·d-1 and enzymatic activity of CYP1A2 isoform increased significantly by 1.65,2.26 and 2.89 times when the doses of Astragalus injection were 0.16,0.8 and 4 g·kg-1·d-1.However,enzymatic activities of CYP2D1,CYP2C6 and CYP2C11 isoforms were not induced by the two kinds of drugs.Conclusions Astragalus granules and Astragalus injection supress enzymatic activities of CYP2D6 and CYP2C19 while increase enzymatic activity of CYP1A2 in rats.