基于质谱技术的代谢组学在体外药物肝毒性评价中的研究进展

Mass Spectrometry-Based Metabolomics in the Study of in vitro Drug Hepatotoxicity Evaluation

药物肝毒性是药物安全性评价的重要内容之一,研发早期对药物及其代谢产物潜在的肝毒性进行准确预测和评价,可以提高药物研发的成功率。将代谢组学技术与体外细胞模型相结合,以细胞代谢表型的变化为指标直接反映药物的毒性效应及毒性机制,能够改善临床前药物肝毒性的预测准确性,在药物肝毒性筛选研究中极具应用价值和发展潜力。本文综述了目前肝毒性研究中的细胞模型与培养方法,介绍了三维细胞培养模型在体外研究中的优势,并总结了基于质谱技术的代谢组学研究在体外细胞模型中的分析策略及其在药物肝毒性评价中的应用,其中基于质谱成像技术的空间分辨代谢组学方法在体外细胞模型研究中具有独特优势,有望发展成为体外肝毒性研究的有力工具。

Hepatotoxicity of drugs is one of the important contents of drug safety evaluation.The accurate evaluation of potential hepatotoxicity of drugs and their metabolites in the early research and development is of great significance to improve the success rate of new drugs.Metabolomics technology combined with in vitro cell model can directly reflect the toxic effect and toxic mechanism of drugs by the change of cell metabolic phenotype,and can improve the prediction of preclinical drug hepatotoxicity,which has great application value and development potential in drug hepatotoxicity screening.This paper reviewed the current cell models and culture methods in hepatotoxicity research,introduced the advantages of 3D cell models in vitro studies,and summarized mass spectrometry-based metabolomics strategy in cell model and its application in the evaluation of drug hepatotoxicity.Among them,the spatially resolved metabolomics method based on mass spectrometry imaging technology has unique advantages in the study of cell models in vitro,which is expected to become a useful tool for the study of hepatotoxicity in vitro.