1,3,8-三羟基-5-甲氧基口山酮对细胞色素P450酶的抑制作用

Inhibition of 1,3,8-trihydroxy-5- methoxyxanthone on cytochrome P450s

目的:在人肝微粒体中研究1,3,8-三羟基-5-甲氧基山口山酮(1,3,8-trihydroxy-5-methoxyx-anthone,TMX)对细胞色素P450酶(CYP450s)的抑制作用。方法:研究加入TMX后,微粒体内主要药物代谢酶活性的变化情况。微粒体孵化体系中各探针药物及其代谢产物的含量用高效液相色谱法测定,酶活性用探针药物的代谢产物浓度与母药浓度的比值表示。结果:加入TMX前后CYP1A2,CYP2C9,CYP2C19,CYP2E1,CYP3A4活性改变[均值(95%可信区间)]分别为2.95×10-3(2.03×10-3,3.88×10-3),3.14×10-2(1.87×10-2,4.42×10-2),2.27×10-3(-1.4×10-2,1.81×10-2),7.72×10-2(-0.83×10-2,0.2374),-0.2548(-2.9802,2.4707)。CYP1A2,CYP2C9的活性变化差异有统计学意义。结论:10μmol/L的TMX在体外对CYP1A2和CYP2C9有显著性抑制作用,对CYP2C19,CYP2E1和CYP3A4的抑制作用并不明显。

Objective To explore the inhibitive effects of 1, 3, 8-trihydroxy-5- methoxyxanthone （TMX） on cytochrome P450s （CYP450s） in human liver microsomes. Methods Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography. Results The variations （ mean, 95 % CI ） of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 × 10^-3 （2.03 × 10^-3, 3.88 × 10^-3） , 3.14 × 10^-2 （1.87 × 10^-2, 4. 42 × 10^-2）, 2. 27 × 10^-3 （ - 1.4 × 10^-2,1. 81 × 10^-2）, 7. 72 × 10^-2 （ -0.83 × 10^-2, 0.2374） , and -0.2548 （ -2. 9802, 2. 4707） , respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX. Conclusion TMX （ 10 μmol/L） has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2 E 1 and CYP3A4.