建立具有药物代谢酶CYP2C9活性的微生物模型  

Establishment of a Microbial Model with the Activity of Drug-Metabolizing Enzyme CYP2C9

作　　者：杨秀伟[1] 黄海华[2] 张鹏[3] 林立红[2] 钟大放[3] 

机构地区：[1]吉林大学生命科学学院,长春130023 [2]沈阳药科大学微生物学教研室,沈阳110016 [3]沈阳药科大学药物代谢与药物动力学实验室,沈阳110016

出　　处：《中国药学杂志》2006年第7期551-555,共5页Chinese Pharmaceutical Journal

基　　金：国家863计划课题(2003AA2Z347C)

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。OBJECTIVE To investigate the ability of Curmingharnella 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 （glibmide, diclofenac and indomethaein） 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. Glybttride, diclofenae and indomethaein were transtbrmed 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 Cunrtinghamella blakesleana AS 3.910 could be used as a suitable microbial model for CYP2C9.

关 键 词：短刺小克银汉霉AS 3.910 微生物转化 液相色谱-质谱 格列本脲 双氟芬酸 吲哚美辛 

分 类 号：Q559.9[生物学—生物化学] R917[医药卫生—药物分析学]