基于数据非依赖型采集质谱技术的血液脂质分子高通量分析

脂质是生物体的重要代谢分子,参与重要的细胞生物功能,已有报道表明环境中污染物会干扰生物体正常循环及代谢机制,导致脂肪代谢紊乱。基于数据非依赖型(DIA)采集质谱技术,通过优化UPLC-QTOF MS(超高效液相色谱飞行时间质谱联用)液相分离方法,开发了少量人体血液样品中脂质代谢分子的高通量分析方法,并将其应用于57个普通人群的血液样品分析,在10μL人体血液样品中检出2 598个信号,经脂代组学质谱库匹配解析鉴定出八大类1 780个脂质分子,其中分子数目占比最大的脂质为甘油磷脂类(37%),其次依次为脂肪酸类(23%)、固醇脂类(13%)、甘油脂类(10%)、鞘脂类(9.0%)、孕烯醇酮脂类(4.8%)。上述研究建立的脂质分子高通量分析方法为以脂质代谢为毒性终点的污染物毒性筛查和毒理机制研究提供方法学基础。

High Throughput Screening of Lipid Metabolites in Blood Based on the Data-independent Acquisition Mode

Lipid is a group of key components in biological processes and comprises diverse classes of molecules with critical functions in cellular energy storage, structure and signaling. It has been reported that environmental pollutants could interfere with the normal circulation and metabolism of biochemical molecular, leading to a disorder of lipid metabolism in organisms. In this study, a high throughput analytical method for lipid metabolites was developed based on UPLC-QTOF MS (ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry) in the data-independent acquisition mode (DIA). The method was applied for analysis of lipid metabolites in human blood samples from a general population. 2 598 signals were detected and 1 780 lipid molecules were identified by the method. Of all the detected lipid metabolites, glycerol phospholipid is the predominant component (37%), followed by fatty acids (23%), sterol lipids (13%), glycerol lipids (10%), sphingolipids (9.0%), pregnenolone lipids (4.8%). The high throughput method established in this study provided an analytical technology for exploring the toxicology pathways of environmental pollutants, which could cause disorder of lipid metabolism to organisms.