孙佳;陆苑;潘洁;郑林;黄勇;王永林;李勇军;
SUN Jia;LU Yuan;PAN Jie;ZHENG Lin;HUANG Yong;WANG Yonglin;LI Yongjun;Engineering Research Center of Ministry of Education for the Development and Application of Ethnic Medicine and TCM,Guizhou Medical University;Guizhou Provincial Key Laboratory of Pharmaceutics,Guizhou Medical University;School of Pharmacy,Guizhou Medical University;National Engineering Research Center of Miao's Medicines,Guizhou Medical University;

• 1: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
• 2:贵州医科大学贵州省药物制剂重点实验室
• 3:贵州医科大学药学院
• 4:贵州医科大学国家苗药工程技术研究中心

摘要(Abstract)：

目的:考察参芎葡萄糖注射液对人肝微粒体细胞色素P450(CYP450)酶6种亚型CYP1A2、CYP2E1、CYP2C9、CYP2C19、CYP2D6、CYP3A4的体外抑制作用。方法:在人肝微粒体孵育系统中,将不同浓度的参芎葡萄糖注射液和7种混合探针底物(非那西丁、氯唑沙宗、甲苯磺丁脲、奥美拉唑、右美沙芬、睾酮和咪达唑仑)共同孵育,采用超高效液相色谱-串联质谱法(UPLC-MS/MS)同时测定孵育液中CYP1A2、CYP2E1、CYP2C9、CYP2C19、CYP2D6和CYP3A4酶对应代谢物(对乙酰氨基酚、6-羟基氯唑沙宗、羟基甲苯磺丁脲、5-羟基奥美拉唑、右啡烷、6β-羟基睾酮和α-羟基咪达唑仑)的剩余量,与对照组进行比较,得到酶的剩余活性,用Graph Pad v5.0软件计算半抑制浓度(IC50)值,考察参考葡萄糖注射液对人肝微粒体CYP450酶的抑制程度。结果:在人肝微粒体孵育体系中,参芎葡萄糖注射液对6种CYP450亚型酶的IC50值均>15%。结论:在临床剂量下,参芎葡萄糖注射液对人肝微粒体CYP1A2、CYP2E1、CYP2C9、CYP2C19、CYP2D6和CYP3A4无明显抑制作用。
Objective: To evaluate the in vitro inhibition effects of Shenxiong glucose injection on 6cytochrome P450 isoforms( CYP1A2,CYP2E1,CYP2C9,CYP2C19,CYP2D6 and CYP3A4) in human liver microsome. Methods: Shenxiong glucose injection were incubated with human liver microsomes in the presence of 7 probe substrates for CYP450 isoforms,including phenacetin for CYP1A2,chlorzoxazone for CYP2E1,tolbutamide for CYP2C9,omeprazole for CYP2C19,dextromethorphan for CYP2D6,testosterone and midazolam for CYP3A4. Meanwhile,UPLC-MS / MS was adopted to measure remaining content of corresponding metabolite of CYP1A2, CYP2E1, CYP2C9, CYP2C19,CYP2D6 and CYP3A4( Acetaminophen,chlorzoxazone 6-hydroxylation,hydroxytolbutamide,5-hydroxy omeprazole,dextrorphan,6 beta hydroxy testosterone and alpha hydroxy midazolam of midazolam). By comparison with control group,the remaining enzyme activities of cytochrome P450 isoforms were calculated. IC50 values were calculated by Graph Pad v5. 0 program to evaluate the inhibitory effects. Results: IC50 values of Shenxiong glucose injection on CYP1A2, CYP2E1, CYP2C9,CYP2C19,CYP2D6 and CYP3A4 were more than 15%. Conclusion: Shenxiong glucose injection don't show inhibitory effect on CYP1A2,CYP2E1,CYP2C9,CYP2C19,CYP2D6 and CYP3A4 in human liver microsome.

关键词(KeyWords)： 参考葡萄糖注射液;细胞色素P450;微粒体,肝;药物相互作用
shenxiong glucose injection;cytochrome P450;microsomes,liver;drug interaction

Abstract:

Keywords:

基金项目(Foundation): 国家科技支撑计划课题(2013BAI11B01);; 贵州省科技重大专项项目[黔科合重大专项字(2011)6019号];; 贵州省中药现代化科技产业研究开发专项[黔科合ZY字(2013)3020号;黔科合中药字(2013)5062号];贵州省中药现代化科技产业研究开发专项[黔科合重G字(2013)4001]

作者(Author): 孙佳;陆苑;潘洁;郑林;黄勇;王永林;李勇军;
SUN Jia;LU Yuan;PAN Jie;ZHENG Lin;HUANG Yong;WANG Yonglin;LI Yongjun;Engineering Research Center of Ministry of Education for the Development and Application of Ethnic Medicine and TCM,Guizhou Medical University;Guizhou Provincial Key Laboratory of Pharmaceutics,Guizhou Medical University;School of Pharmacy,Guizhou Medical University;National Engineering Research Center of Miao's Medicines,Guizhou Medical University;

Email:

DOI: 10.19367/j.cnki.1000-2707.2016.07.007

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