早期冠状动脉粥样硬化患者血浆代谢组学研究  

Study on Plasma Metabolomics of Patients With Early-stage Coronary Atherosclerosis

作　　者：孙萌[1] 刘伟[1] 刘海霞[1] 于波[1] SUN Meng;LIU Wei;LIU Haixia;YU Bo(Department of Cardiology,The Second Affiliated Hospital of Harbin Medical University,The Key Laboratory of Myocardial Ischemia,Harbin(150081),Heilongjiang,China)

机构地区：[1]哈尔滨医科大学附属第二医院心内科心肌缺血教育部重点实验室,黑龙江省哈尔滨市150081

出　　处：《中国循环杂志》2022年第1期24-30,共7页Chinese Circulation Journal

基　　金：黑龙江省普通本科高等学校青年创新人才培养计划(UNPYSCT-2016192)。

摘　　要：目的:通过代谢组学方法研究早期冠状动脉粥样硬化患者血浆内源性代谢物的变化,寻找与该疾病密切相关的生物标志物。方法:选取经冠状动脉造影确诊的患者120例,分为早期冠状动脉粥样硬化组[定量分析(QCA)测定冠状动脉狭窄<50%,n=60]和对照组(冠状动脉造影未发现任何可辨认的斑块或狭窄,n=60),采用液相色谱-四级杆飞行时间质谱(liquid chromatography quadrupole time-of-flight mass spectrometry,LC-QTOF/MS)联用技术对所有患者的血浆样品进行非靶向代谢组学分析,利用多变量结合单变量统计分析方法筛选差异代谢物。结果:早期冠状动脉粥样硬化组和对照组的血浆代谢轮廓呈现明显分离,表明两组代谢物发生了显著变化。正、负离子模式下,共筛选并鉴定出42个差异代谢物。与对照组相比,早期冠状动脉粥样硬化组血浆中鞘氨醇、棕榈酸、磷脂酰胆碱(PC)(14:0/14:0)和甘油单酯(MG)(18:2)等24种代谢物的含量显著升高,而溶血磷脂酰胆碱(LysoPC)(18:1)、溶血磷脂酰乙醇胺(LysoPE)(18:2)、磷脂酰甘油(PG)(18:0/0:0)和甘油二酯(DG)(36:3)等18种物质的含量明显降低。结论:基于LC-QTOF/MS的代谢组学方法是发现早期冠状动脉粥样硬化潜在生物标志物的有效手段。这些标志物不仅加深了对冠状动脉粥样硬化发病机制的认识,还为疾病的早期诊断和治疗提供了新的思路与方法。Objectives:To analyze the changes of metabolites in the plasma of patients with early coronary atherosclerosis using metabolomics,and to explore the potential biomarkers for identifying early-stage coronary atherosclerosis.Methods:A total of 120 patients confirmed by coronary angiography were selected and divided into early coronary atherosclerosis group(n=60)and control group(n=60).Non-targeted metabolomics analysis was performed on plasma samples by liquid chromatography combined with quadrupole time-of-flight mass spectrometry(LC-QTOF/MS).Univariate and multivariate statistical analysis were performed to identify potential biomarkers for patients with early-stage coronary atherosclerosis.Results:There were clear separations on plasma metabolites profile between the early-stage coronary atherosclerosis patients and controls,indicating significant changes in metabolites between the two groups.A total of 42 potential endogenous biomarkers were identified in both positive and negative ion modes.Compared to the controls,the plasma levels of 24 metabolites such as sphingosine,palmitic acid,PC(14:0/14:0)and MG(18:2)were significantly higher,while the levels of 18 metabolites such as LysoPC(18:1)、LysoPE(18:2)、PG(18:0/0:0)and DG(36:3)were lower in patients with early coronary atherosclerosis.Conclusions:Our study demonstrates that plasma metabolomics analyzed by LC-QTOF/MS possess great potential in identifying biomarkers for early-stage coronary atherosclerosis.These biomarkers could not only provide more information for further understanding of the metabolic processes of coronary atherosclerosis,but also be helpful for the diagnosis and treatment of patients with early-stage coronary atherosclerosis.

关 键 词：早期冠状动脉粥样硬化 代谢组学 生物标志物 液相色谱-四级杆飞行时间质谱 

分 类 号：R54[医药卫生—心血管疾病]