大鼠肝微粒体cyp2c9酶活性测定中影响因素的研究.doc

大鼠肝微粒体法评价20种中药有效成分对CYP2C9酶的作用 张远冬1，刘学庆1，郭延垒2，张有金2，石亮2，王二豪2，于超* （1、重庆医科大学公共卫生学院生殖生物学研究室；2、生命科学研究院，重庆 400016） 摘要目的方法37 oC水浴温孵冰乙腈终止反应，HPLC产物4＇-羟基双氯酸结果4＇-羟基双氯酸mol·min-1·mg -1)，其显著低于对照组735.8±17.27(pmol·min-1·mg-1，P＜0.05），其他实验组与对照组比较，其转化率无明显统计学差异。结论CYP2C9酶关键词CYP2C9；中药有效成分 Effects of CYP2C9 activities in rat live microsomes by 20 active constituents of chinese herbal drugs Zhang Yuandong1，L Xueqing1，G Yanlei2，Z Youjing2，Siang2，W Erhao2，Yu Chao* (1、Reproductive Biology Laboratory，School of Public Health；2、Institute of Life Sciences，Chongqing Medical University，400016，China)Abstract] Objective The study was to establish a method for evaluating the activity of cytochrome P450 2C9 using diclofenac as the probe compound in rats liver microsomes (RLM) in vitro, and investigate the impact of 20 active constituents of chinese herbal drugs on CYP2C9 activity. Methods Diclofenac and 20 active constituents of chinese herbal drugs were incubated with rat liver microsomes for 15 min at 37 oC, and the reaction was terminated by cold acetonitrile, and the theconvert ratio of 4＇-Hydroxydiclofenac determined by HPLC. Finally, the effects of 20 active constituents of chinese herbal drugs on CYP2C9 activities was evaluated by compaired theconvert ratio with control group. Results Among the 20 active constituents, Baicalein, Cnidiadin, Emodin, Swertiamarin, Icariin, Resveratrol were found to have a strong inhibition on CYP2C9 with theconvert ratio of 402.6±10.58, 210.9±10.26, 414.5±10.32, 509.8±26.45, 355.4±15.87, 387.3±22.16(pmol·min-1·mg-1), which were significantly lower than control group735.8±17.27(pmol·min-1·mg-1, P＜0.05Conclusion The method of rats liver microsomes for evaluating influence of active constituents of chinese herbal drugs on CYP2C9 activity was successfully established. Baicalein, Cnidiadin, Emodin, Swertiamarin, Icariin, Resveratrol have inhibited CYP2C9 activity in vitro, which indicated we should to pay a ttention to the drug-drug interactions when these active consti