Cocktail探针药物法评价生、醋莪术对CYP450酶亚型的影响  

Application of probe drugs for detecting influences of Rhizoma Curcumae and processed Rhizoma Curcumae on cytochrome P450 isoforms

作　　者：王菊[1] 陆兔林[1,2] 毛春芹[1] 肖永庆[3] 顾娟娟[1] 

机构地区：[1]国家教育部中药炮制规范化及标准化工程研究中心国家中医药管理局中药炮制标准重点研究室江苏省中药炮制重点实验室,江苏南京210046 [2]南京中医药大学药学院,江苏南京210046 [3]中国中医科学院中药研究所,北京100700

出　　处：《中国药理学通报》2012年第11期1562-1565,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81173548);江苏省教育厅重大项目(No 09KJA360001);中国中医科学院中药研究所自主选题(No 2011ZDXK-02)

摘　　要：目的用Cocktail探针药物法,研究生、醋莪术对大鼠CYP1A2、CYP3A4和CYP2E1活性的影响并进行比较,探讨其通过炮制增强或改变作用的趋向性。方法将SD大鼠随机分组,生、醋莪术组分别给予生、醋莪术提取液(9 g.kg-1),以生理盐水为空白对照,在一定时间点采集血样,用HPLC检测探针药物在大鼠体内的代谢情况,以评价生、醋莪术对CYP450酶的影响。结果生莪术的茶碱、氨苯酚和氯唑沙宗的代谢情况与空白组相比差异无显著性;但醋莪术与空白组相比,茶碱和氯唑沙宗的T12、Tmax和AUC明显增加,CL/F明显降低;氨苯酚的T12变化不明显,AUC明显降低,CL/F明显增加;氯唑沙宗的T12、Tmax、AUC明显增加,CL/F明显降低。结论单次给予大鼠生、醋莪术后,生莪术对CYP450酶的作用不明显,醋莪术对CYP1A2和CYP2E1具有抑制作用,对CYP3A4具有诱导作用。Aim To research and compare the influences of Rhizoma Curcumae and processed Rhizoma Curcumae on the cytochrome P450 isoforms,and to explore the tropism processed of Rhizoma Curcumae to enhance or change the role.Methods Rats were randomly divided into three groups.The treatment groups were received Rhizoma Curcumae and processed Rhizoma Curcumae respectively.The other group were received saline as blank control group.Blood samples were collected at different time points and the plasma concentration of cocktail probe drugs was determined by HPLC.Results There was insignificant difference of the ophylline,dapsone,chlorzoxazone between the Rhizoma Curcumae group and the blank group.Compared with the blank group,the half-life time,Tmax and the area under curve increased significantly and the clearance lowered significantly of ophylline and chlorzoxazone in the processed Rhizoma Curcumae group;There was insignificant difference in the half-life time of dapsone,the area under curve lowered significantly and the clearance increased significantly in the processed Rhizoma Curcumae group.Conclusion Rhizoma Curcumae has no significant effect on the cytochrome P450 isoforms of CYP1A2,CYP3A4 and CYP2E1.But the processed Rhizoma Curcumae can inhibit CYP1A2 and CYP2E1 and has an inductive effect on the CYP3A4.

关 键 词：COCKTAIL 莪术 CYP450 CYP1A2 CYP3A4 CYP2E1 

分 类 号：R-332[医药卫生] R282.71