探针药物法评价不同羟基位点苯乙酸对4种肝微粒体酶的代谢影响  

Evaluation of the effect of phenylacetic acid with different hydroxyl sites on the metabolism of four liver microsomal enzymes by probe drug method

作　　者：康超 郝督 简思杰 荣娜 刘祥 丁锐 KANG Chao;HAO Du;JIAN Si-jie;RONG Na;LIU Xiang;DING Rui(Sino German Institute of Natural Products,School of Bioscience and Engineering,Shaanxi University of Technology,Hanzhong 723000,China;Gansu New Hope Liuhe Agriculture and Animal Husbandry Co.Ltd,Lanzhou 730000,China)

机构地区：[1]陕西理工大学生物科学与工程学院中德天然产物研究所,陕西汉中723000 [2]甘肃新希望六和农牧有限公司,甘肃兰州730000

出　　处：《陕西理工大学学报（自然科学版）》2021年第1期50-56,78,共8页Journal of Shaanxi University of Technology:Natural Science Edition

基　　金：国家外国专家局项目(GDT20186100426);陕西省教育厅科学研究计划项目(17JK0137);陕西理工大学人才启动项目(SLGQD1803)。

摘　　要：通过钙沉淀法制备大鼠肝微粒体,将3-羟基苯乙酸、4-羟基苯乙酸、3,4-二羟基苯乙酸与4种亚型酶(CYP1A2、CYP2C9、CYP2E1和CYP3A4)的特异性探针药物(非那西丁、甲苯磺丁脲、氯唑沙宗、睾酮)在体外孵育,应用高效液相色谱法检测探针底物浓度,间接获得相对酶活性和计算半数抑制浓度(IC 50),从而对不同羟基位点苯乙酸对大鼠肝微粒体主要的CYP450酶系活性进行评价。发现不同羟基位点苯乙酸对大鼠肝微粒体主要的4种CYP450酶无抑制作用,药效作用安全,可为药物合成奠定基础。This experiment,through the preparation of rat liver microsomal calcium precipitation,will be a 3-hydroxy benzene acetic acid,4-hydroxy benzene acetic acid,3,4-2hydroxy benzene acetic acid with four subtypes enzyme(CYP1A2,CYP2C9,CYP2E1 and CYP3A4)specific probe drugs(phenacetin,tolbutamide,chlorzoxazone and testosterone)in vitro incubation,and apply high performance liquid chromatography(HPLC)technique to the detection of probe substrate concentration,thus indirectly gain relative enzyme activities and calculate the half inhibitory concentration(IC 50),so that an evaluation of the activity of CYP450 enzyme system at different hydroxyl site phenylacetic acid on rat liver microsomal.It has been found that phenylacetic acid at different hydroxyl sites has no inhibitory effect on four major CYP450 enzymes in rat liver microsomes,and its pharmacodynamic effect is safe,laying a foundation for drug synthesis.

关 键 词：苯乙酸 细胞色素P450 肝微粒体 抑制作用 

分 类 号：R965.3[医药卫生—药理学]