探针药物法评价黄草乌酒对大鼠肝脏CYP1A2、CYP3A1和CYP2E1的影响

发布时间：2018-01-08 17:37

  本文关键词：探针药物法评价黄草乌酒对大鼠肝脏CYP1A2、CYP3A1和CYP2E1的影响　出处：《河南科技大学学报(医学版)》2016年04期 　论文类型：期刊论文

  更多相关文章： 黄草乌 酒精 Cocktail探针药物 CYP UPLC-MS/MS

【摘要】：目的探讨黄草乌酒对大鼠CYP450亚型(CYP1A2、CYP3A1、CYP2E1)的代谢活性的影响。方法采用Cocktail探针法(咖啡因、咪达唑仑和氯唑沙宗),利用超高效液相色谱—串联质谱(UPLC-MS/MS)测定黄草乌酒对大鼠CYP450亚型活性影响。将大鼠随机分为5组,分别为空白对照组、白酒组、单草乌组、低草乌酒组和高草乌酒组,各组动物连续灌胃给药14 d,于第15 d腹腔注射Cocktail探针药液,并于腹腔注射探针药液前后不同时间点断尾采血。使用UPLC-MS/MS测定各探针药物的血药浓度,评价CYP450亚型的代谢活性。结果氯唑沙宗的半衰期(T1/2)均低于空白对照组(P0.05),表明酒精、黄草乌和黄草乌酒对CYP2E1均有明显的诱导作用。与空白对照组相比,酒精对CYP1A2和CYP3A1的诱导不明显。与白酒组相比,黄草乌酒对CYP3A1和CYP2E1的诱导以及对CYP1A2的抑制作用均无显著性差异。结论黄草乌与酒精合用后可诱导CYP2E1的活性,发生药物间相互作用,增加黄草乌对大鼠的肝毒性。
[Abstract]:Objective to investigate the effect of Huangcaowu wine on the metabolic activity of CYP1A2CY CYP2E1, a subtype of CYP450 in rats. Methods the method of Cocktail probe (caffeine) was used. Midazolam and chlorzoxazone were used to determine the effect of Huangcaowu wine on the activity of CYP450 subtype in rats by UPLC-MS / MS. The rats were randomly divided into 5 groups. The rats were divided into three groups: blank control group, liquor group, single Aconitum group, low Caowu liquor group and high Caowu liquor group. The animals in each group were intraperitoneally injected with Cocktail probe solution for 14 days. Blood samples were collected at different time points before and after intraperitoneal injection of probe solution. Blood concentration of each probe was measured by UPLC-MS/MS. Results the half-life of clozoxazone was significantly lower than that of control group (P 0.05), indicating alcohol. Compared with the blank control group, the induction of CYP1A2 and CYP3A1 by alcohol was not obvious, and that of the liquor group was higher than that of the liquor group. There was no significant difference in the induction of CYP3A1 and CYP2E1 and the inhibitory effect on CYP1A2. Conclusion the activity of CYP2E1 can be induced by the combination of Acanthopsis flavescens and alcohol. To increase the hepatotoxicity of Atractylodes flavescens to rats by drug interaction.
【作者单位】： 昆明医科大学法医学院;昆明医科大学第一附属医院;
【基金】：云南省应用基础研究基金资助项目(2013FB118) 云南省教育厅科学研究基金(2014Y161)
【分类号】：D919
【正文快照】： However,the inductions of alcohol were notobvous on CYP1A2 and CYP3A1.Compared withthe white spirit group,the inductions of aconitumvilmorimianum kom liquor on CYP3A1 andCYP2E1 were no significant,as well as theinhibition on CYP2E1.Conclusion Aconitumvil，

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