MicroRNAs表达与药物代谢酶CYP2C19活性相关性研究

Relationship between microRNAs expression and drug metabolism enzyme CYP2C19 activity

目的探讨肝组织MicroRNAs(miRNA)与CYP2C19代谢酶活性的相关性。方法通过基于LC/MS/MS的"Cocktail"探针药物法检测人肝S9中CYP2C19等4种代谢酶活性;运用生物信息学预测软件选择5个作用于CYP2C19 mRNA的miRNA以及1个作用于CYP3A4 mRNA的miRNA作为阴性对照,并用qRT-PCR方法检测其在肝组织中的表达水平,分析miRNA表达量与酶活性的关系。结果在6个miRNAs中,miR-130a(r=-0.476 2,P<0.05)和miR-142(r=-0.400 8,P<0.05)在肝脏中的表达水平与CYP2C19酶活性显著负相关。结论 miRNA的表达水平可能是影响人群中CYP2C19酶活性变化差异的重要因素之一。

Objective To investigate the correlation between miRNAs expression and cytochrome CYP2C19 enzyme activity in liver tissues. Methods The activities of four metabolic enzymes in liver S9 fraction including CYP2C19 were determined by cocktail drug probe approach based on LC / MS / MS. Five potential miRNAs targeting CYP2C19 mRNA and one negative miRNA targeting CYP3A4 mRNA were chosen by bioinformatics software. The levels of these miRNAs in liver were determined by qRT-PCR. The relevance between miRNAs expression and metabolic enzyme activities was analyzed. Results Among the six miRNAs,miR-130a（ r =-0.476 2,P 0.05） and miR-142（ r =-0.400 8,P 0.05） levels were negatively associated with the activity of CYP2C19. Conclusion miRNAs could be one of key factors that influence CYP2C19 activity in populations.