[关键词]
[摘要]
目的 研究丹参酮IIA、隐丹参酮和丹参酮I组合物(组合物)在斑马鱼体内的代谢,探讨斑马鱼用于中药多组分代谢研究的可行性及合理性。方法 将斑马鱼暴露于组合物1% DMSO纯净水溶液中,采用高效液相色谱-电喷雾离子阱质谱(HPLC-MS)检测,根据准分子离子峰获得代谢物相对分子质量信息,通过与文献数据或对照品比较,鉴定组合物暴露于斑马鱼24 h后的药液及鱼体中的代谢产物。结果 组合物经斑马鱼作用后,产生丹参酮IIA和隐丹参酮的羟基化和脱氢产物,未发现丹参酮I的代谢产物。结论 斑马鱼对组合物的代谢与大鼠或鼠肝微粒体的代谢机制高度一致,提示斑马鱼对该组合物的代谢具合理性,且具有化合物用量少、成本低、简单、高效等优点,为斑马鱼用于更复杂的中药体系代谢研究提供依据。
[Key word]
[Abstract]
Methods To investigate the in vivo metabolism of the combination of tanshinone IIA (Tan IIA), cryptotanshinone (Cry), and tanshinone I (Tan I) in zebrafish and discuss the possibility and rationality of using zebrafish in multi-component metabolism of Chinese materia medica (CMM). Methods The zebrafish was exposed to the 1% DMSO solution of the combinations with Tan IIA, Cry, and Tan I. High performance liquid chromatography coupled with ion-trap mass spectrometry (HPLC-MS) method was used to calculate the relative molecular weight of the metabolites based on the excimer ion peak. The metabolites in solution and zebrafish after the combination being exposed to zebrafish for 24 h were identified through comparing with the literature data and reference substances. Results After the combination being exposed to zebrafish, hydroxylation and dehydrogenation products of Tan IIA and Cry were obtained while the metabolites of Tan I was not found. Conclusion The metabolic mechanism of zebrafish against the combination highly consists with those in rats or rat liver microsomes, which indicates that the metabolism of zebrafish against the combination is rational with the advantages of less amount of compound, lower cost, simpler operation, and higher efficiency. The above results provide the reference for using zebrafish in the metabolic study on complex CMM system.
[中图分类号]
[基金项目]
国家自然科学基金资助项目(30973978);江苏省中医药领军人才项目(2006)