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目的:观察人肝微粒体CYP2A6动力学特征.方法:采用生化分析法,体外研究化学异物对CYP2A6酶活性的影响.测定香豆素7-羟化酶的动力学参数.同时分析CYP2A6与Ⅱ相酶UGT之间的相关性.结果:CYP2A6活性差异8.8倍,K_m和V_(max)分别为0.25-1.56μmol·L~(-1)、1.41-8.70μmol·min~(-1)·g~(-1).匹鲁卡品、二乙基二硫代氨基甲酸盐、利福平明显抑制CYP2A6活性,IC_(50)值分别为 5.31μmol·L~(-1)、156.35μmol·L~(-1)和38.81μmol·L~(-1).α-萘黄酮、磺胺苯吡唑、醋竹桃霉素、酮康唑、泼尼松龙和阿奇霉素对香豆素7-羟化反应几乎无影响.CYP2A6与UGT_2之间存在显著相关性(r=0.9453,P<0.05).结论:中国人细胞色素P4502A6酶活性及动力学参数存在个体差异,CYP2A6与UGT_2之间有显著相关.除匹鲁卡品有CYP2A6选择性抑制作用外,利福平和二乙基二硫代氨基甲酸盐也明显抑制CYP2A6活性.
OBJECTIVE: To observe the kinetic characteristics of CYP2A6 in human liver microsome.METHODS: The effects of chemical foreign bodies on the activity of CYP2A6 were studied in vitro by biochemical methods.Kinetic parameters of coumarin 7-hydroxylase were assayed.At the same time, CYP2A6 and Ⅱ phase The results showed that the activity of CYP2A6 was 8.8-fold different, K_m and V_max were 0.25-1.56μmol·L -1, 1.41-8.70μmol · min -1 · g -1, (-1) .Pilocarpine, diethyldithiocarbamate and rifampin significantly inhibited the activity of CYP2A6 with IC 50 values of 5.31μmol·L -1 and 156.35μmol·L -1, respectively ~ (-1) and 38.81μmol·L ~ (-1) respectively.α-naphthoflavone, sulfaphenazole, vinegaromycin, ketoconazole, prednisolone and azithromycin coumarin 7-hydroxylation There was a significant difference between CYP2A6 and UGT_2 (r = 0.9453, P <0.05) .Conclusion: There are individual differences in cytochrome P4502A6 activity and kinetic parameters between Chinese and CYP2A6, and there is a significant correlation between CYP2A6 and UGT_2. In addition to pilocarpine CYP2A6 selective inhibition, rifampin and diethyldithiocarbamate also significantly inhibited CYP2A6 activity.