【摘要】 为了研究乙醇对鲫鱼细胞色素P450 2E1(CYP2E1)活性的影响,用药动学方法,以氯唑沙宗为底物探针,将130尾鲫鱼随机分为试验组和对照组2组,试验组鲫鱼每日经口灌服乙醇1 g/kg,对照组灌服相同剂量的生理盐水,连续5 d后,第6天2组鲫鱼同时一次性腹腔注射氯唑沙宗10 mg/kg,于注射后不同时间采血,用高效液相色谱法测定氯唑沙宗在鲫鱼体内不同时间点的血药浓度,并计算药动学参数。结果表明,氯唑沙宗在两组鲫鱼体内的药时数据均符合二室模型;与对照组相比,乙醇处理组氯唑沙宗的半衰期增加了0.9倍(P<0.01),药时曲线下面积增加了0.8倍(P<0.01),总清除率减少了51.2%(P<0.01)。提示乙醇对鲫鱼CYP2E1的活性具有显著的抑制作用。更多还原

【Abstract】 The effect of ethanol(EtOH) on the activity of cytochrome P450 2E1 in Carassius auratus was investigated by pharmacokinetics with chlorzoxazone(CZX) as a specific substrate.130 fish were equally divided into two groups:EtOH-treated group and the control group.EtOH was administered orally to fish at the dose of 1 g/(kg·d) for 5 consecutive days.Fish in control group received an equal volume of normal saline only.On the 6th day,two groups of fish were given an intraperitoneal injection with 10 mg/kg CZX.The plasma concentrations of CZX were determined by HPLC,and the pharmacokinetic parameters were calculated.The results showed that the concentration-time data of CZX in two groups both fitted two compartment models.Compared with the saline-treated control group,elimination half life was increased by 0.9 fold(P<0.01),area under the curve was increased by 0.8 fold(P<0.01),and total clearance was shortened by 51.2%(P<0.01) in the EtOH-treated group.The results indicated that the activity of CYP2E1 could be obviously inhibited by EtOH.更多还原