非那西丁探针法动态观测非酒精性脂肪肝大鼠发病进程中的CYP1A2活性  

Dynamic Observation of CYP1A2 Activity in Nonalcoholic Fatty Liver Disease Process of Rats by Phenacetin Probe Method

作　　者：刘莹[1] 金涌[1] 蒋培培[1] 吴德敏[1] 方慧子[2] 周静婷[2] 季俊虬 

机构地区：[1]安徽医科大学药学院,合肥230032 [2]安徽医科大学第一临床学院,合肥230032 [3]安徽立方药业有限公司,合肥230088

出　　处：《中国药房》2012年第17期1559-1561,共3页China Pharmacy

基　　金：安徽医科大学七年制临床医学专业“早期接触科研”训练计划(2011-ZQKY-91)课题资助项目

摘　　要：目的:建立探针法动态观测非酒精性脂肪肝大鼠发病进程中细胞色素(CY)P450酶系的活性。方法:制备非酒精性脂肪肝大鼠模型,分别于造模后第0、7、9、11、13、15、17周给予探针药物非那西丁并收集尿液,检测其中非那西丁代谢产物对乙酰氨基酚的各代谢指标以考察CYP1A2的活性变化情况,同时设立正常大鼠组为对照。含量检测采用高效液相色谱法,色谱柱为HypersilODS,流动相为甲醇-水(12.5∶87.5),流速为1.0 mL.min-1,检测波长为254 nm。结果:对乙酰氨基酚的单位体重代谢量在第9周时达到最高,明显高于第0周和正常组((15.02±3.12)、(10.03±3.60)、(9.96±4.00)mg.kg-1),随后又逐渐降低,即CYP1A2的活性先升高后降低。结论:建立的探针法简便可靠,适用于大鼠尿中对乙酰氨基酚的测定以及CYP1A2活性的研究。OBJECTIVE： To observe the activity of CYP450 in nonalcoholic fatty liver disease process of rats by phenacetin probe method dynamically.METHODS： Nonalcoholic fatty liver rat model was established,and probe drugs were given at 0th,7th,9th,11th,13th,15th,17th week and at the same time urine was collected.The metabolism index of phenacetin metabolite acetaminophen was determined to investigate the activity of CYP1A2 acetaminophen with normal rats as control.HPLC method was used.The determination was performed on Hypersil ODS column with mobile phase consisted of methanol-water（12.5 ∶ 87.5） at the flow rate of 1.0 mL·min-1.The detection wavelength was set at 254 nm.RESULTS： The metabolism of acetaminophen per unit body weight reached the peak at 9th week,which is higher than at 0th week and normal group（（15.02±3.12）,（10.03±3.60）,（9.96±4.00） mg·kg-1）,and then decreased gradually,i.e.the activity of CYP1A2 increased firstly and then decreased.CONCLUSION： This method is simple and reliable for the determination of acetaminophen in rats urine and CYP1A2 activity research.

关 键 词：探针法 高效液相色谱法 非酒精性脂肪肝模型 大鼠 CYP1A2 非那西丁 对乙酰氨基酚 

分 类 号：R965[医药卫生—药理学]