基于二维亲水-反相色谱质谱联用的磷脂组学平台应用于II型糖尿病合并冠心病相关的生物标志物的筛查

项目名称： 基于二维亲水-反相色谱质谱联用的磷脂组学平台应用于II型糖尿病合并冠心病相关的生物标志物的筛查

项目编号： No.81202502

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 朱超

作者单位： 德州学院

项目金额： 23万元

中文摘要： 磷脂组学是对生物体内磷脂化合物全面的定性定量，其关键是建立快速、稳定、高通量的检测方法。由于磷脂分子结构的相似性，借助一维色谱难以实现不同类和同类不同分子磷脂的同时分离。本研究将首次基于二维亲水-反相色谱质谱联用技术（2D HILIC-RPLC/MS）建立新型磷脂检测平台，获取磷脂轮廓谱，实现磷脂的高效分离和定量。新型磷脂组学平台将用于疾病相关的生物标志物的筛查,为代谢组学研究提供新工具。糖尿病及其合并症的病理过程"脂毒性→糖尿病→脂代谢紊乱→糖尿病慢性合并症"显示脂代谢紊乱贯穿疾病发生发展的整个过程。有着良好预警能力的脂质标志物有助于糖尿病及其合并症的诊断和疗效评价。糖尿病合并冠心病（DCHD）不易发现且死亡率高，因此，本研究将借助新型磷脂组学平台筛查DCHD相关的生物标志物。通过分析动物模型和临床患者的磷脂轮廓谱及生化指标找出具有临床应用性的生物标志物，从而促进实验室研究向临床的转化。

中文关键词： 磷脂组学；糖尿病合并冠心病；二维亲水桥流反相色谱质谱联用；ZDF大鼠；整合分析

英文摘要： Phospholipidomics, which focuses on comprehensive qualification and quantitation of phospholipids in bio-samples, requires a rapid, robust and high throughput measuring platform. Due to the similarity of phospholipids structure, an efficient between-group and within-group separation of phospholipids is difficult to be simultaneously achieved by one dimensional liquid chromatography. In this study, a novel separation method based on two dimensional LC(2D HILIC-RPLC)-MS for profiling and quantitation of phospholipids will be developed,to our best knowledge, for the first time. This phospholipdomics platform will be applied to discover biomarkers of disease supplying a new tool for metabolomics study.The pathological process "Lipotoxicity→DM→Disorder of lipid metabolism→Complications of DM" indicates that lipid metabolism disorder happens throughout the whole progress of DM and its complications. Therefore, some lipid biomarkers with high predictability are beneficial to diagnosis and therapeutic evaluation of diabetes and its complications. Patients that have diabetic coronary heart disease (DCHD) are difficult to diagnose and have high mortality, and our study therefore aims to discover biomarkers of DCHD by using the novel phospholipidomics platform. The biomarkers that can be used for clinical research applicat

英文关键词： Phospholipidomics；Diabetic coronary heart disease；2D HILIC-Bridge current-RPLC-TOFMS；ZDF rat；Integrated analysis