人肝微粒体CYP2C19酶基因多态性对奥美拉唑代谢的影响  

Effect of CYP2C19 polymorphism on omeprazole metabolism in liver microsome

作　　者：李赛非 周军[2] 孟凡民[2] 

机构地区：[1]郑州大学,郑州450052 [2]郑州大学人民医院麻醉科

出　　处：《医药论坛杂志》2015年第4期20-23,共4页Journal of Medical Forum

摘　　要：目的通过以肝功能正常的人肝标本为研究对象,考察CYP2C19基因多态性对酶代谢探针药物奥美拉唑的影响。方法收集60例功能正常的人肝组织,提取肝微粒体,选取奥美拉唑为CYP2C19的探针药物,采用高效液相色谱法检测其代谢产物5-羟基奥美拉唑,计算酶动力学参数Km、Vmax、CLint;并提取DNA,采用聚合酶链反应-限制性片断长度多态性方法检测CYP2C19基因型。结果酶动力学参数Km、Vmax、CLint数值及范围的分别是56.33（27.56-192.3）μM、96.61（11.35-381.4）pmol/（min·mg）protein和1.82（0.19-7.46）μl/（min·mg）protein,Km、Vmax、CLint个体间差异达分别为6.9、33.6、39.3倍;与野生型＊1＊1相比,突变杂合型＊1＊2和突变纯合型＊2＊2 CLint明显降低（P〈0.05）。结论人肝微粒体CYP2C19对奥美拉唑的代谢呈现出较大的个体差异;CYP2C19＊2突变明显降低其代谢活性。Objective To investigate the effect of geno polymormism of CYP2C19 on omeprazole metabolism in liver mi- erosome. Methods Normal liver samples was collected （ n = 60）. To extract mierosome and genome DNA. To deter- mine the concentration of 5 - hydroxyomeprazole by High Performance Liquid Chromatography. Polymerase chain reaction - restriction fragment length polymorphism was used to detect the genotypes of CYP2C19. Results The media and range of Km, Vmax, CLint were 56. 33 （27.56 - 192. 3） μM, 96.61 （ 11.35 - 381.4） pmol/（ min · mg） protein, 1.82 （0. 19 -7.46） μl/（min · mg）protein, respectively. The variation of Kin, Vmax, CLint were 6. 9, 33.6, 39 - fold difference, respectively. The CLint of ＊ 1 ＊ 2 and ＊ 2 ＊ 2 was significant decrease compared with the ＊ 1 ＊ 1 （ P 〈 0. 05）. Conclusion There were significant individual variation of the CYP2C19 activity to metabolize omeprazole in liver mierosome. The allele ＊ 2 cause the enzyme activity decreased.

关 键 词：细胞色素P450 2C19 奥美拉唑 活性 基因多态性 体外代谢 

分 类 号：R969.1[医药卫生—药理学]