MicroRNAs as biomarkers for drug-induced liver injury

由于与肝毒性相关的严重不良反应，几种药物已被从药品市场上撤下。在大多数情况下，肝毒性的机制尚不清楚，也缺乏预测性的实验动物模型。因此，药物性肝损伤的实验动物模型将能够为预测性毒性研究进行全面的分析。MiRNA在外源和内源物质的代谢以及毒理学方面的研究只是最近才建立起来的。我们开展了以下研究：(1)氟烷诱导的小鼠肝损伤模型的建立及miRNA在早期肝损伤中的作用；(2)免疫相关因子和miRNA在双氯芬酸诱导的小鼠肝损伤模型中的作用；(3)氟氯西林诱导的小鼠肝损伤模型的建立；(4)大鼠肝细胞损伤、胆汁淤积和脂肪变性模型中血浆microRNA的变化。(5)过氧酶体增殖物-激活剂受体。在人肝脏中受miR-21和miR-27b调控

Because of the significant adverse drug reactions associated with hepatotoxicity, several drugs have been removed from the pharmaceutical market. In most cases, the mechanisms of the hepatotoxicity are unknown and predictive experimental animal models are lacking. Thus, experimental animal models of drug-induced liver injury will enable to perform comprehensive analyses for predictive toxicity studies. The miRNA research in the metabolism of xenobiotics and endobiotics and in toxicology has only recently been established. We performed studies with the following titles,(1) Establishment of halothane-induced liver injury in mice and involvement of miRNA on early onset of liver injury.(2) Involvement of immune-related factors and miRNA in the mouse model of diclofenac-induced liver injury.(3) Establishment of the mouse model of flucloxacillin-induced liver injury.(4) Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis.(5) Peroxisome proliferator-activator receptor. is regulated by miR-21 and miR-27b in human liver