乙醇对鲫鱼CYP2E1活性的影响

Effect of ethanol on activity of cytochrome P450 2E1 in Carassius auratus

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。

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 e- qually 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.