参芎葡萄糖注射液对肝脏6种亚型微粒体细胞色素P450酶的抑制作用  

In vitro Inhibition Effects of Shenxiong Glucose Injection on 6 Cytochrome P450 Isoforms in Human Liver Microsome

作　　者：孙佳[1,2,3,4] 陆苑[2,3] 潘洁[3] 郑林[2,3] 黄勇[2,3] 王永林[2,3] 李勇军[1,3] 

机构地区：[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,贵州贵阳550004 [2]贵州医科大学贵州省药物制剂重点实验室,贵州贵阳550004 [3]贵州医科大学药学院,贵州贵阳550004 [4]贵州医科大学国家苗药工程技术研究中心,贵州贵阳550004

出　　处：《贵阳医学院学报》2016年第7期775-778,共4页Journal of Guiyang Medical College

基　　金：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]

摘　　要：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。[ Abstract]Objective：To evaluate the in vitro inhibition effects of Shenxiong glucose injection on 6 cytochrome P450 isoforms（ CYP1 A2 ,CYP2 E1 ,CYP2 C9 ,CYP2 C19 ,CYP2 D6 and CYP3 A4 ）in hu-man liver microsome. Methods：Shenxiong glucose injection were incubated with human liver micro-somes in the presence of 7 probe substrates for CYP450 isoforms,including phenacetin for CYP1A2, chlorzoxazone for CYP2 E1 ,tolbutamide for CYP2 C9 ,omeprazole for CYP2 C19 ,dextromethorphan for CYP2D6,testosterone and midazolam for CYP3A4. Meanwhile,UPLC-MS/MS was adopted to meas-ure remaining content of corresponding metabolite of CYP1 A2 , CYP2 E1 , CYP2 C9 , CYP2 C19 , CYP2D6 and CYP3A4（ Acetaminophen,chlorzoxazone 6-hydroxylation,hydroxytolbutamide,5-hy-droxy omeprazole,dextrorphan,6 beta hydroxy testosterone and alpha hydroxy midazolam of midazo-lam）. By comparison with control group,the remaining enzyme activities of cytochrome P450 isoforms were calculated. IC_50 values were calculated by GraphPad v5. 0 program to evaluate the inhibitory effects. Results：IC_50 values of Shenxiong glucose injection on CYP1A2, CYP2E1, CYP2C9, CYP2 C19 ,CYP2 D6 and CYP3 A4 were more than 15%. Conclusion：Shenxiong glucose injection donˊt show inhibitory effect on CYP1 A2 ,CYP2 E1 ,CYP2 C9 ,CYP2 C19 ,CYP2 D6 and CYP3 A4 in human liver microsome.

关 键 词：参考葡萄糖注射液 细胞色素P450 微粒体 肝 药物相互作用 CYTOCHROME P450 

分 类 号：R969.2[医药卫生—药理学]