【摘要】 目的研究短刺小克银汉霉AS 3.910体外模拟人体细胞色素P450(CYP)2C9的能力,建立具有CYP2C9活性的微生物模型。方法选用3种人体CYP2C9代谢的药物格列本脲、双氯芬酸和吲哚美辛为底物,利用液相色谱-质谱联用技术检测药物代谢产物的种类和转化率。结果通过调节转化培养基的种类和初始pH,使转化系统在较高底物浓度下具有良好的转化效果,格列本脲、双氯芬酸和吲哚美辛总转化率分别为90%,100%和83%,而且形成的主要转化产物与人体CYP2C9产生的主要代谢产物相同。结论短刺小克银汉霉AS 3.910具有CYP2C9代谢酶活性,是研究人体CYP2C9药物代谢适宜的体外模型。更多还原

【Abstract】 OBJECTIVE To investigate the ability of Cunninghamella blakesleana AS 3.910 to mimic cytochrome P450(CYP) 2C9 in human,and build the microbial model of CYP2C9.METHODS Three drugs metabolized by CYP2C9(gliburide,diclofenac and indomethacin) were used as substrates.Their metabolites and transformation yields were detected by liquid chromatography-mass spectrometry.RESULTS The microbial system reached high transformation levels by changing the medium and original pH.Glyburide,diclofenac and indomethacin were transformed by C.blakesleana AS 3.910,with a total transformation ratio of 90%,100% and 83%,respectively.Their major metablites were same as that in human.CONCLUSION Cunninghamella blakesleana AS 3.910 could be used as a suitable microbial model for CYP2C9.更多还原