药源性肝损伤潜在血清生物标志物的研究进展

Progress in potential candidate serum biomarker of drug-induced liver injury

近年来,生物标志物的研究已成为药物临床前安全性评价中发展最快的领域。在药物的使用过程中,机体受药物或其代谢产物的毒性作用,或过敏反应而引发肝损伤。传统的肝损伤诊断指标主要依靠血清肝功能检测(如丙氨酸氨基转移酶、门冬氨酸氨基转移酶、碱性磷酸酶等),但这些传统指标在特异性和敏感性方面都存在一定的局限性。近几年,对肝损伤相关的新的潜在生物标志物,如微小RNA-122、α-谷胱甘肽-S转移酶、对氧磷酶、嘌呤核苷磷酸化酶、苹果酸脱氢酶、T-激肽原等的研究越来越多。本文对近期国内外较新的药源性肝损伤的血清生物标志物进行简述。

In the recent years , the research about biomarkers of drug-induced liver injury is a rapid development area in drugs ＇preclinical safety evaluation and assessment .During the process of taking drugs , the organism received toxicities of drugs and /or its metabolites , or anaphylaxis to lead to liver injury .The traditional biomarkers for assessing liver injury is based primarily on the detection of hepatic enzymes in blood, such as alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, alkaline phosphate（ALP） et al. However, elevation of blood hepatic enzymes has limitations in specificity and sensitivity .Recently, there are many results about the candidate serum biomarkers of liver injury have been reported , such as miRNA-122, α-glutathione-S-transferase（α-GST）, paraoxonase （PON-1）, purine nucleoside phosphorylase（PNP）, malate dehydrogenase（MDH）, thiostatin et al.This review was designed to assess the value of potential biomarkers for improving the detection of liver injury .