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目的:研究葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)模型大鼠不同病期肝、肾、肠微粒体中奥美拉唑(OME)代谢酶活性的变化。方法:DSS诱导UC急性期(UCA)和恢复期(UCR)大鼠模型。同时制备UCA、UCR以及正常对照(NOR)组大鼠的肝、肾、肠微粒体。将不同浓度的OME与微粒体共孵育,用LC/MS/MS检测样品中5-OH OME的生成量,比较OME在各组微粒体中的代谢活性。结果:连续饮用5%DSS 7 d,UCA和UCR组大鼠表现出明显的结肠炎症状。DSS停药后7 d,UCR组大鼠症状有所好转。UCA组肝微粒体中5-OH OME的生成速率低于NOR组,UCR组的生成速率恢复到正常水平。UCA组的CLint与NOR组相比降低了45%。OME在3组大鼠肾和肠微粒体中的代谢活性无显著差异。结论:OME在肝微粒中的代谢会受到UC的影响而改变,可能会影响到OME在患者体内的药动学。
OBJECTIVE: To study the changes of omeprazole (OME) metabolizing enzyme activity in liver, kidney and intestine microsomes of rats with ulcerative colitis (UC) induced by dextran sodium sulfate (DSS). Methods: DSS induced UC (UCA) and convalescent (UCR) rat models. At the same time, liver, kidney and intestinal microsomes of UCA, UCR and normal control (NOR) rats were prepared. Different concentrations of OME were incubated with microsomes, the amount of 5-OH OME in the sample was measured by LC / MS / MS, and the metabolic activity of OME in each group of microsomes was compared. Results: After continuous drinking of 5% DSS for 7 days, the rats in UCA and UCR group showed obvious symptoms of colitis. After 7 days of DSS withdrawal, the symptoms of UCR rats improved. The generation rate of 5-OH OME in liver microsomes of UCA group was lower than that of NOR group, and the generation rate of UCR group returned to normal level. The CLint in the UCA group decreased by 45% compared to the NOR group. There was no significant difference in the metabolic activity of OME in the kidney and gut microsomes of the three groups. CONCLUSIONS: The metabolism of OME in liver microgranules may be affected by UC and may affect the pharmacokinetics of OME in patients.