广藿香醇在体外对人肝微粒体中CYP3A4的非竞争性抑制作用研究  

Noncompetitive inhibition effect of patchouli alcohol on CYP3A4 of human liver microsome in vitro

作　　者：武梦琳 秦崇臻 柴玉娜[1] 卢瑶瑶 汪新茹 张晶敏[1] 齐光照 WU Meng-lin;QIN Chong-zhen;CHAI Yu-na;LU Yao-yao;WANG Xin-ru;ZHANG Jing-min;QI Guang-zhao(Department of Pharmacy,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052)

机构地区：[1]郑州大学第一附属医院药学部,郑州450052

出　　处：《中南药学》2021年第10期2082-2086,共5页Central South Pharmacy

基　　金：国家自然科学基金青年项目(No.81703780);2021年度河南省重点研发与推广专项(科技攻关)项目(No.212102310348)。

摘　　要：目的通过体外药物代谢实验探讨广藿香醇对CYP450活性的影响,并探讨其作用机制。方法使用人肝微粒体与广藿香醇孵育的体外方法,测定其IC_(50)值以及K_(i)值,推测其可能的作用机制;并通过CYP3A4重组酶进行验证。结果广藿香醇呈浓度依赖性抑制体外人肝微粒体咪达唑仑代谢,其 IC_(50)为5.195 μmol·L^(-1) ,根据Lineweaver-Burk作图以及二次作图,计算其K_(i)为 0.86 μmol·L^(-1) ,并判断广藿香醇对CYP3A4的抑制属于非竞争性抑制类型。结论广藿香醇在体外可抑制人肝微粒体CYP3A4活性,与经由CYP3A4代谢的化学药物联用时,可能产生药物相互作用。Objective To determine the inhibitory effect of patchouli alcohol(PA)on CYP450 activity of human liver microsome and its possible mechanism in vitro.Methods After the incubation of PA and human liver microsome system,the IC_(50) and K_(i) values were determined,and its mechanism was speculated.Moreover,cDNA-expressed CYP3A4 was used to identify the selective inhibition.Results PA strongly inhibited CYP3A4 activity in a dose-dependent manner with IC_(50)5.195μmol·L^(-1) in human liver microsome.The typical Lineweaver-Burk plots and secondary plots showed that PA inhibited CYP3A4 activity noncompetitively,with a K_(i) value at 0.86μmol·L^(-1) in human liver microsome.Conclusion PA can inhibit CYP3A4 activity in vitro and may lead to drug interactions by CYP3A4 with other drug combinations.

关 键 词：CYP3A4 广藿香醇 肝微粒体 抑制 酶促动力学 

分 类 号：R965[医药卫生—药理学]