口服黄芩素对大鼠药物代谢酶的影响  

Drug interaction potential of oral baicalein on metabolic enzymes in rats

作　　者：田硕[1] 何国荣[1] 高梅[1] 孙加琳[1] 王夙博[1] 杜冠华[1] 

机构地区：[1]北京协和医学院,中国医学科学院药物研究所,药物靶点研究与新药筛选北京市重点实验室,北京100050

出　　处：《中国新药杂志》2012年第19期2230-2234,2301,共6页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2009ZX09302-003)

摘　　要：目的:考察口服黄芩素对大鼠肝细胞色素P450(CYP450)、谷胱甘肽-S-转移酶(GST)和尿苷二磷酸-葡萄糖醛酸转移酶(UGT)活性的影响。方法:大鼠连续7 d口服200 mg.kg-1黄芩素后,差速离心法制备肝微粒体和肝胞浆,采用特异性探针底物法测定肝微粒体CYP450酶系6种同工酶活性的变化,采用比色法检测GST和UGT活性的变化。结果:大鼠口服黄芩素对CYP2C9,CYP2E1,GST和UGT有显著的抑制作用,抑制率分别为26.76%,29.12%,37.45%和70.86%(P<0.05或0.01),对CYP1A2,CYP2C19,CYP2D6和CYP3A4没有明显的影响。结论:其他药物与黄芩素合用时,需考虑可能由于代谢酶活性变化引起的药物相互作用。Objective： To study the interaction potential of oral baicalein on main metabolic enzymes, including six hepatic CYP450 isoforms, GST and UGT. Methods： Hepatic microsomes and cytoplasm were prepared by a differential centrifugation method after oral administration of baicalein at 200 mg·kg^-1 for 7 days in rats. Specific substrates were used as probes of six CYP450 isoforms to describe the activities of CYP450 isoforms. The ac- tivities of GST and UGT were detected by a colorimetric method. Results： Repeated dosing of baicalein showed a significant inhibition of CYP2C9, CYP2E1, GST and UGT in 37.45% and 70.86% （P 〈0.05 or 0.01）, respectively. CYP2C19, CYP2D6 and CYP3A4 were observed. Conclusion zymes indicates that potential drug-drug interaction may occur rats. The inhibition rates were 26.76% , 29.12% , No significant effects on the activities of CYP1A2, ： The inhibition of baicalein on several metabolic enwhen baicalein administered with other drugs

关 键 词：黄芩素 细胞色素P450(CYP450) 谷胱甘肽-S-转移酶(GST) 尿苷二磷酸-葡萄糖醛酸转移 酶(UGT) 药物相互作用 

分 类 号：R96[医药卫生—药理学]