摘要
采用鸡尾酒法(cocktail)探究糖皮质激素诱导的肾阳虚抑郁症状态大鼠体内6种CYP450亚型酶活性变化。连续21天肌注氢化可的松,建立肾阳虚抑郁症大鼠模型;分别选用甲苯磺丁脲、氯唑沙宗、茶碱、咪达唑仑、奥美拉唑和右美沙芬作为CYP2C6、CYP2E1、CYP1A2、CYP3A2、CYP2D1、CYP2D2探针底物。采用液质联用法(LC-MS/MS)测定空白组和模型组大鼠体内6种混合探针的血药浓度,计算药动学参数。与空白组相比,模型组大鼠体内茶碱、氯唑沙宗和甲苯磺丁脲的代谢显著加快(P<0.01),右美沙芬、奥美拉唑、咪达唑仑的代谢无显著差异。结果表明氢化可的松诱导的肾阳虚抑郁模型CYP2E1、CYP1A2和CYP2C6均被诱导。
This study was designed to explore the impact of depression on kidney-yang deficiency in rats. Rats were repeatedly injected with hydrocortisone for 21 days to establish the depression model with kidney- yang deficiency. Tolbutamide,chlorzoxazone,theophylline,midazolam,omeprazole and dextromethorphan were used as substrates of CYP2C6,CYP2E1,CYP1A2,CYP3A2,CYP2D1,and CYP2D2 to test the depression impact on drug metabolism. Plasma concentrations of six CYP450 were determined by LC-MS/MS and used as pharmacokinetic parameters. Consequently,metabolism of theophylline,chlorzoxazone and tolbutamide were accelerated significantly in the model relative to the control（P〈0.01）,but dextromethorphan,omeprazole and midazolam did not exhibit a significant difference. The present study suggests that depression with kidney- yang deficiency had a strong induction of CYP2E1 and moderate induction of CYP1A2,CYP2C6 in the rat model.
出处
《药学学报》
CAS
CSCD
北大核心
2017年第2期258-263,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81573685)
江苏省中药资源产业化过程协同创新中心重点项目(ZDXM-2)
