基于脂质组学技术研究急性缺血性脑卒中临床诊断标志物

Diagnostic Biomarker Study on Early Detection of Acute Ischemic Stroke Via Lipidomics Technology

目的:急性缺血性脑卒中(Acute ischemic stroke, AIS)是由于血流减少导致的脑功能突然丧失。由于AIS发病机制是异质性和多因素的,我们建立全面的脂质组学方法来阐明AIS进程相关的脂质变化和复杂的脂质代谢网络。方法:选取26例AIS患者血液标本和27例健康志愿者血清作为研究对象,进行总脂抽提,通过基于LC-MS策略的非靶向脂质组学方法进行规模性、整体性的脂质组学分析。结果:对AIS患者和健康志愿者血浆进行大规模脂质定性定量分析,通过Progenesis~? QI软件分析Xevo~? G2-XS QTOF质谱系统MSE采集的子离子数据,精确定量到1054个脂质特征差异,准确定性得到368个脂质分子,多变量统计分析中差异脂质组成能将AIS患者和健康志愿者区分开来,通路富集分析图显示差异脂质主要参与甘油磷脂代谢的紊乱。结论:AIS患者血浆脂质组成与健康志愿者存在显著差异,差异表达的脂质可能与AIS发生有关。这些发现有助于开发新的诊断标志物和AIS治疗靶点。

Objective: Acute ischemic stroke is a sudden loss of brain function due to the reduction of blood flow. The pathogenesis of AIS is heterogeneous and multifactorial, hence we establish comprehensive lipidomic approach to explore altered lipid composition and complex metabolic networks associated with acute ischemic stroke. Methods: Serum samples containing 26 AIS patients and 27 healthy volunteers were collected as subjects. Total lipid extraction was performed, and large-scale lipid species were analyzed via non-targeted lipidomics based on LC-MS strategy. Results: Large-scale lipidomic qualitative and quantitative analysis of plasma, comparing AIS patients with healthy controls, via MSE scan by Xevo~? G2-XS QTOF mass spectrometry system and peak alignment and deconvolution by Progenesis~? QI software. A total of 1054 lipid characteristics were accurately quantified and 368 lipid molecules were precisely identified. Multivariate statistical analyses unraveled that altered lipid composition distinguished AIS patients from healthy controls. The pathway enrichment analysis showed that the significantly changed lipids were mainly involved in glycerophospholipid metabolism disorders. Conclusions: Our lipidomic data showed a strikingly consistent separation between AIS patients and healthy donors. Decipherment of lipid compositions distinguishing AIS from control can lead to identify critical diagnostic biomarkers as well as develop therapeutic targets for AIS progression.