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采用鸡尾酒(cocktail)探针药物法研究慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)造成的抑郁状态对大鼠体内6种CYP450亚酶活性的影响。根据Katz法建立CUMS大鼠抑郁模型;分别选用甲苯磺丁脲、氯唑沙宗、茶碱、咪达唑仑、奥美拉唑及右美沙芬作为大鼠CYP2C6、CYP2E1、CYP1A2、CYP3A2、CYP2D1、CYP2D2的探针底物,采用液质联用法(LC-MS/MS)测定对照组与模型组大鼠体内6种混合探针的血药浓度,计算药动学参数。结果表明,茶碱和氯唑沙宗代谢显著加快(P<0.01),甲苯磺丁脲、右美沙芬、奥美拉唑、咪达唑仑的代谢无显著差异。结果说明,慢性不可预见性温和应激造成的抑郁状态对CYP1A2有强诱导、对CYP2E1有中强诱导作用。
To investigate the effects of chronic unpredictable mild stress (CUMS) on the activities of six CYP450 enzymes in rats using cocktail probe method. The depression model of CUMS rats was established according to the method of Katz. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were selected as the rats’ CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 , CYP2D2 probe substrate, using liquid chromatography-mass spectrometry (LC-MS / MS) determination of the control group and model rats in vivo 6 kinds of mixed probe blood concentration, calculate pharmacokinetic parameters. The results showed that the metabolism of theophylline and chlorzoxazone was significantly accelerated (P <0.01), and there was no significant difference in metabolism between tolbutamide, dextromethorphan, omeprazole and midazolam. The results show that chronic unpredictable mild stress caused by the state of depression CYP1A2 have a strong induction of CYP2E1 have a strong induction.