非酒精性脂肪性肝病(nonalcoholic fatry liver disease,NAFLD)是一种常见慢性肝脏疾病,其发病率呈逐年上升趋势,但发病机制尚未明确,诊疗手段仍不完善.蛋白质组学(proteomics)的出现使NAFLD研究有了进一步的发展,相关研究已达21个.目前,蛋白质组学技术可以研究疾病相关的分子改变,从而寻找新的生物标志物和治疗靶标.在此,对蛋白质组学在NAFLD诊断及分期、发病机制和其他相关领域研究进展作一个较为全面的综述.首先,对研究中遇到的研究对象、样本种类、实验方法和标志物特征选择进行经验性总结.其次,除了介绍如何运用蛋白质组学研究病因、危险因素和重要分子在NAFLD发病机制中的作用,还介绍NAFLD发病机制的亚细胞蛋白质组学、修饰蛋白质组学以及蛋门质组学与转录组学相结合的研究实例.此外,对差异蛋白质的分析策略和价值作了重点闸述,收集到一些有望成为NAFLD治疗靶标的候选分子.最后,结合新技术展望研究新空间,以期能够有助于推动蛋白质组学在寻找新的疾病标志物、探索疾病分子机制和治疗靶标中开辟新的途径.
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with an increasing morbidity. However, its pathogenesis is still elusive and its diagnosis and treatment need to be improved. The emergence of proteomics has pushed NAFLD research forward and twenty-one associated studies have been reported by now. Recent progress in proteomic techniques allows evaluation of molecular changes associated with disease, thereby permitting to identify novel biomarkers and therapeutic targets. Herein, the application of proteomics in the study of the diagnosis, pathogenesis and other related fields of NAFLD were comprehensively reviewed. Firstly, empirical knowledge about categories of subjects and samples, experimental methods and biomarker selection was summarized. Secondly, in addition to studies utilizing proteomics to explore roles of etiological factors, risk factors and important molecules in the pathogenesis of NAFLD, studies of NAFLD pathogenesis by the means of subcellular proteomics, modification-specific proteomics, and the integration of proteomics and transcriptomics were also shown. Thirdly, methods for analyzing differentially expressed proteins and implications of these results were highlighted. It's hoped that this review can help to promote the application of proteomics in exploring disease pathogenesis and discovering novel biomarkers and treatment targets.