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目的采用模式生物斑马鱼研究5-羟基黄酮的代谢,探索斑马鱼用于药物Ⅱ相代谢的适用性。方法将斑马鱼培养于5-羟基黄酮溶液中,定时取鱼体及药液,采用高效液相色谱-电喷雾质谱联用检测,根据正、负离子模式准分子离子峰获得化合物分子量信息,通过与文献数据或对照品对照,结合碎片离子,推测可能的代谢产物。结果在斑马鱼体内或体外药液检测到5-羟基黄酮原型及其2个单羟基葡萄糖醛酸结合物和1个单羟基硫酸结合物。结论 5-羟基黄酮在斑马鱼作用下的葡萄糖醛酸化反应与其在大鼠体内的Ⅱ相代谢机制高度一致,并首次在负离子模式下检测到5-羟基黄酮硫酸结合物。斑马鱼用于药物Ⅱ相代谢具合理性,且具有化合物用量少、成本低、方法简单、高效的优势,为建立斑马鱼体内药物代谢新模型提供重要参考。
Objective To study the metabolism of 5-hydroxyflavone by using model organism zebrafish and to explore the applicability of zebrafish for metabolism of drug phase Ⅱ. Methods The zebrafish were cultured in 5-hydroxyflavone solution, the fish and the solution were taken regularly, and the compound molecular weight information was obtained from the quasi-molecular ion peak of positive and negative ion mode by high performance liquid chromatography-electrospray ionization mass spectrometry. Literature data or reference control, combined with fragment ions, speculated that the possible metabolites. Results Prototypes of 5-hydroxyflavone and two monohydroxyalkanoic acid conjugates and one monohydroxy sulfate conjugate were detected in zebrafish in vivo or in vitro. Conclusions The glucuronidation of 5-hydroxyflavone in zebrafish is highly consistent with its phase II metabolism in rats, and the first time the 5-hydroxy flavone sulfate conjugate was detected in negative ion mode. The zebrafish has the advantages of being rational for phase II drug metabolism, has the advantages of less dosage, low cost, simple and high efficiency, and provides an important reference for establishing a new model of drug metabolism in zebrafish.