丹参酮Ⅱ_A、隐丹参酮和丹参酮Ⅰ组合物在斑马鱼体内的代谢研究  

In vivo metabolic study on combination of tanshinone Ⅱ_A,cryptotanshinone, and tanshinone Ⅰ in zebrafish

作　　者：韦英杰[1] 贾晓斌[1] 詹扬[1] 王长梅[1] 马文泉 王兵 徐丽丽 

机构地区：[1]江苏省中医药研究院国家中医药管理局中药口服释药系统重点研究室,江苏南京210028 [2]潍坊高新区生物医药科技产业园,山东潍坊261061

出　　处：《中草药》2013年第9期1149-1156,共8页Chinese Traditional and Herbal Drugs

基　　金：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)

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。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 nmlti-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 zehrafish, 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 studv on comnlex CMM svstem.

关 键 词：丹参酮ⅡA 隐丹参酮 丹参酮Ⅰ 斑马鱼 代谢 高效液相色谱-电喷雾离子阱质谱 

分 类 号：R965.2[医药卫生—药理学] R969.1[医药卫生—药学]