艾迪注射液对大鼠原代肝细胞中CYP1A2、CYP3A2酶活性的影响  

Effects of Aidi Injection on CYP1A2 and CYP3A2 enzyme activities in primary rat hepatocytes

作　　者：陆苑[1,2,3] 潘洁 杨淑婷[1,2] 刘亭 李勇军 孙佳[1,2] LU Yuan;PAN Jie;YANG Shu-ting;LIU Ting;LI Yong-jun;SUN Jia(Guizhou Provincial Key Laboratory for Pharmaceutics,Guizhou Medcial University,Guiyang 550004,China;School of Pharmaceutical Sciences,Guizhou Medcial University,Guiyang 550004,China;National Engineering Research Center of Miao’s Medicines,Guizhou Medical University,Guiyang 550004,China;Ministry of Education Engineering Research Center for the Development and Application of Ethnic Medicine and TCM,Guizhou Medcial University,Guiyang 550004,China)

机构地区：[1]贵州医科大学,贵州省药物制剂重点实验室,贵州贵阳550004 [2]贵州医科大学药学院,贵州贵阳550004 [3]贵州医科大学,国家苗药工程技术研究中心,贵州贵阳550004 [4]贵州医科大学,民族药与中药开发应用教育部工程研究中心,贵州贵阳550004

出　　处：《中成药》2018年第9期1920-1925,共6页Chinese Traditional Patent Medicine

基　　金：贵州省中药现代化科技产业研究开发专项项目(黔科合ZY字[2013]3020);贵州省科技厅联合基金项目(黔科合LH字[2015]7361);贵阳市科技计划项目(筑科合同[20141001]09);大学生创新创业训练计划项目(201510660006);贵州省科学技术厅人。才团队项目(黔科合平台人才[2016]5613\5677)。

摘　　要：目的评价艾迪注射液对大鼠原代肝细胞中CYP1A2、CYP3A2酶活性的影响。方法采用两步胶原酶循环灌流法分离大鼠原代肝细胞,建立体外肝细胞温孵体系,选择非那西丁、咪达唑仑分别作为CYP1A2、CYP3A2的探针药物,建立同时测定肝细胞中代谢物对乙酰氨基酚、α-羟基咪达唑仑的UPLC-MS/MS法。将阳性诱导剂奥美拉唑和苯巴比妥、不同浓度艾迪注射液、空白溶剂分别作用肝细胞2 d,给予探针药物孵育60 min后,测定各探针代谢物生成量,计算相对阳性对照活性,评价艾迪注射液对CYP1A2和CYP3A2酶活性的影响。结果艾迪注射液对大鼠原代肝细胞中CYP1A2、CYP3A2亚型酶的相对阳性对照活性均小于40%。结论艾迪注射液对大鼠原代肝细胞中CYP1A2、CYP3A2亚型酶活性无明显影响。AIM To evaluate the effects of Aidi Injection on CYP1A2 and CYP3A2 enzyme activities in primary rat hepatocytes.METHODS The primary rat hepatocytes isolated by two step collagenase perfusion were used to help establish an in vitro hepatocytes warm incubation system,and phenacetin and midazolam were selected as CYP1A2 and CYP3A2 substrates,respectively.The simultaneous determination of acetaminophen,alpha hydroxy midazolam in hepatocytes was accomplished by UPLC-MS/MS method.The primary rat hepatocytes undergone 2-day treatment of omeprazole,or phenobarbital,or multiple concentrations of Aidi Injection were subsequently incubated with the probe drugs for 60 min,and had the amount of metabolites(acetaminophen and alpha hydroxy midazolam)determined,and the relative positive control activity calculated to evaluate the effects of Aidi Injection on CYP1A2 and CYP3A2 enzyme.RESULTS Aidi Injection showed a less than 40%relative positive control activity on CYP1A2 and CYP3A2 isoforms in primary rat hepatocytes.CONCLUSION Aidi Injection has no significant effects on the activity of CYP1A2 and CYP3A2 isoforms in primary rat hepatocytes in vitro.

关 键 词：艾迪注射液 CYP1A2 CYP3A2 原代肝细胞 UPLC-MS/MS 

分 类 号：R285.5[医药卫生—中药学]