蛋白质组学技术在药物性肝损伤生物标志物研究中的应用

Application of proteomics to screening biomarkers of drug-induced liver injury

临床前药物性肝损伤的评价存在灵敏性低和特异性差的问题,常产生假阴性结果和出现意外的毒性,是导致药物终止开发甚至退市的重要原因之一。在药物肝毒性临床前研究中,可以利用蛋白质组学技术的快速、灵敏、高通量等优点,寻找和发现新的肝毒性生物标志物,使药物开发过程更为安全有效。本文对肝毒性生物标志物的研究现状,蛋白质组学在生物标志物的发现及验证等方面的技术发展进行了综述分析,并且着重归纳了该技术在中药致肝损伤方面的生物标志物研究中的应用。与传统评价方法相比,蛋白质组学技术对于发现新型肝潜在毒性生物标志物具有不可替代的优势。随着蛋白质组学技术结合其他组学技术的发展,其在药物肝毒性早期筛选、生物标志物的临床桥接等方面将取得突破性的进展。

The preclinical safety assessment of hepatotoxicity drugs has a low sensitivity and low specificity. Related tests often generate false negative results and unexpected toxicity,which is one of the major reasons for the cessation of development and withdrawal from the market. Proteomics enjoys advantages of rapidness,high sensitivity and high throughout,and therefore can be used in the search for new biomarkers of hepatotoxicity in preclinical studies,leading to the development of safer drugs and a more efficient drug discovery process. In this review,the current preclinical biomarkers of liver toxicity and development of proteomic technologies in the discovery and validation of biomarkers of drug-induced liver injury are described,in general the application of proteomics to Chinese medicine-induced liver toxicity in particular. Compared with traditional methods,proteomic technologies show promising results for the discovery of novel hepatotoxic markers. Proteomics,in conjugation with other omics techniques,will play a major role in the early stage of hepatotoxicity screening and will prove to be a good bridge in clinics in the future.