静脉麻醉和吸入麻醉对CYP2E1的影响

2×2 Latin square design self-control experiment to explore effects of anesthesia on CYP2E1

目的:通过2x2拉丁方设计,采用戊巴比妥钠进行静脉注射,异氟醚进行吸入麻醉,观察麻醉对细胞色素P450亚型2E1(CYP2E1)代谢活力的影响,探索不同麻醉方式对CYP2E1代谢活力的影响。方法:采用静脉注射给予戊巴比妥钠和(或)吸入麻醉异氟醚麻醉大鼠,经高效液相色谱(HPLC)检测CYP2E1的探针药物氯唑沙宗的血浆药物浓度经时变化,从而反映CYP2E1的代谢活力。采用药代动力学分析软件DAS3.0,计算血浆药代谢动力学参数。采用BL-420生物机能系统测定大鼠麻醉状态下的心率。结果:戊巴比妥钠静脉麻醉在0.5 h、1 h、1.5 h、2 h时间点体内探针药物氯唑沙宗浓度明显低于未麻醉组,差异有统计学意义(P<0.05);在2 h、3 h、4 h三个时间点,戊巴比妥钠麻醉组氯唑沙宗代谢物6羟基氯唑沙宗浓度高于未麻醉组,差异具有统计学意义(P<0.05)。戊巴比妥钠麻醉后,探针药物氯唑沙宗在体内浓度与麻醉后心率呈负相关(r=-0.41,P<0.05)。异氟醚吸入麻醉组3 h、4 h、6 h时间点氯唑沙宗血药浓度均高于未麻醉组,差异具有统计学意义(P<0.05,P<0.01);6羟基氯唑沙宗浓度在0.5 h、1 h、1.5 h时间点高于未麻醉组,差异具有统计学意义(P<0.05)。异氟醚麻醉后,探针药物氯唑沙宗在体内浓度与麻醉后心率呈负相关(r=-0.326,P<0.05)。结论:戊巴比妥钠静脉麻醉可诱导CYP2E1活性,加快药物代谢;异氟醚吸入麻醉可抑制CYP2E1活性,减慢药物代谢。麻醉过程中CYP2E1活力与心率呈明显相关性。

Objective:The effect of anesthesia on the metabolic activity of cytochrome P450 subtype CYP2E1 was observed by 2x2 Latin square design,intravenous injection of pentobarbital sodium,and the effects of different anesthesia methods on CYP2E1 metabolic activity were explored.Methods:Rats were anesthetized with intravenous pentobarbital sodium and/or inhaled anesthesia with isoflurane.The plasma drug concentration of CYP2E1 probe drug chlorzoxazone was measured by high performance liquid chromatography(HPLC).Metabolic activity of CYP2E1.The pharmacokinetic parameters were calculated using the pharmacokinetic analysis software DAS3.0.The heart rate of the rats under anesthesia was measured using the BL-420 biological function system.Results:The concentration of the probe drug chlorzoxazone in the intravenous anesthesia of pentobarbital at 0.5 h,1 h,1.5 h,2 h was significantly lower than that in the unanesthetized group.The difference was statistically significant(P<0.05).At 2 h,3 h,4 h,the concentration of chlorzoxazone metabolite 6-hydroxy chlorzoxazone in the pentobarbital sodium anesthesia group was higher than that in the unanesthetized group.The difference was statistically significant(P<0.05).After anesthesia with pentobarbital sodium,the concentration of the probe drug chlorzoxazone was negatively correlated with heart rate after anesthesia(r=-0.41,P<0.05).The concentration of chlorzoxazone in the isoflurane inhalation anesthesia group was higher than that in the unanesthetized group at 3 h,4 h,and 6 h,and the difference was statistically significant(P<0.05).The concentration of 6-hydroxy chlorzoxazone was higher than that of the unanesthetized group at 0.5 h,1 h,and 1.5 h,and the difference was statistically significant(P<0.05).After isoflurane anesthesia,the concentration of the probe drug chlorzoxazone was negatively correlated with heart rate after anesthesia(r=-0.326,P<0.05).Conclusion:Intravenous anesthesia with pentobarbital sodium can induce CYP2E1 activity and accelerate drug metabolism;isoflurane inhalation anesthesia can inhibit CYP2E1 activity and slow drug metabolism.There was a significant correlation between CYP2E1 activity and heart rate during anesthesia.