摘要
目的研究CYP2B6和CYP3A酶活性在肝硬化模型大鼠体内的变化。方法雄性SD大鼠分别采用每周2次ip给予30%CCl4连续7周、饮用含0.03%-0.04%硫代乙酰胺（TAA）液连续10周、复合法（sc给予用花生油配制的40%CCl4＋高脂饲料＋15%乙醇,共6周）及免疫法（sc给予牛血清白蛋白20-40 mg·kg-1,共11周）制备肝硬化模型后,联合ig给予安非他酮15 mg·kg-1和咪达唑仑10 mg·kg-1。测定给药前及给药后0.083,0.25,0.5,1,1.5,2,2.5,3,4,6,8,12和24 h的血药浓度。结果与正常对照组相比,四氯化碳组和TAA组的2个探针药曲线下面积（AUC）均显著性升高（P〈0.05）,峰浓度c max显著性升高（P〈0.01）,清除率Cl/F均显著性下降（P〈0.05）;复合法组2个探针药c max均显著性下降（P〈0.05）;免疫组2个探针药的药代参数均无统计学意义。结论 CCl4和TAA诱导的肝硬化模型大鼠体内CYP2B6和CYP3A酶活性降低。
OBJECTIVE To study the changes of enzyme activity of CYP2B6 and CYP3A in rats with liver cirrhosis. METHODS Fifty male SD rats were randomly divided into five groups（ n = 10） ： normal control（ NC） group,carbon tetrachloride（ CCl 4） group（ the rats were ip given 30% CCl 4 2 mL·kg- 1twice weekly for 7 weeks）,thioacetamide（ TAA） group（ the rats were given 0. 03% TAA in drinking water for 5 weeks and then 0. 04% TAA for another 5 weeks）,composite method（ CM） group（ the rats were sc given 40% CCl 4 once every 3 d and high-fat with 15% alcohol diet） and immune method（ IM） group（ the rats were sc given bovine serum albumin 20-40 mg·kg- 1for 11 weeks）. All these rats were ig administered with amfebutamone 15 mg·kg- 1and midazolam 10 mg·kg- 1. Then,the blood samples（ 0. 3 mL） were collected from the tail vein into heparinized 1. 5 mL polythene tubes at 0. 083,0. 25,0. 5,1, 1. 5,2,2. 5,3,4,6,8,12 and 24 h after administration. The plasma concentrations of amfebutamone and midazolam were measured by LC-MS. RESULTS There was obvious difference in plasma concentrations and corresponding pharmacokinetic parameters of amfebutamone and midazolam in rats after administration. Compared with the NC group,the AUC of two probe drugs increased significantly（ P 0. 05）,so did the c max（ P 0. 01）,while the Cl/F decreased significantly（ P 0. 05） in CCl 4 and TAA groups. In CM group,the c max of two probe drugs decreased significantly（ P 0. 05）. However,pharmacokinetic parameters of two probe drugs in IM group hardly changed compared with the control group. CONCLUSION In CCl 4 and TAA groups,the enzyme activity of CYP2B6 and CYP3A decreases in rats with liver cirrhosis.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2014年第1期81-87,共7页
Chinese Journal of Pharmacology and Toxicology
基金
浙江省科技厅实验动物科技计划项目(2012C37101)
浙江省教育厅科研基金(Y201119284)
温州市科技局科研基金(Y20110160)
温州市科技局科研基金(Y20110134)~~
