在线二维微液相色谱质谱新方法及在2型糖尿病代谢组学研究中的应用

项目名称： 在线二维微液相色谱质谱新方法及在2型糖尿病代谢组学研究中的应用

项目编号： No.20805045

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 石先哲

作者单位： 中国科学院大连化学物理研究所

项目金额： 18万元

中文摘要： 针对目前代谢组学分离技术平台对全组分代谢物分析的局限性和糖尿病代谢组学研究的重要性，本项目首先研制了适合小分子代谢物分析的毛细管整体柱，包括具有疏水反相作用的poly(MAA-co-EDMA)聚合物毛细管整体柱和有机-无机杂化C8毛细管整体柱以及具有亲水作用的聚(SPE-co-EDMA) 毛细管整体柱。在此基础上，构建了HILIC-RPLC二维微柱液相色谱系统、纳升级和微升级的在线富集分析色谱系统以及全二维Ag+ LC×LC液相色谱系统。利用建立的上述分析系统，进行了2型糖尿病大鼠、糖尿病人群以及中药治疗糖尿病的作用机理等代谢组学研究，结果找到12个潜在的糖尿病相关标志物，其中抗坏血酸和去氨基丙二酸标志物是与机体的氧化状态相关的。发现小檗碱可能通过调节糖尿病人的脂肪酸代谢，降低游离脂肪酸的浓度，从而改善胰岛素抵抗，降低血糖的作用。项目完成过程中共发表论文7篇，申请专利2件，培养在读研究生4名，博士毕业1名。

中文关键词： 多维色谱;质谱;代谢组学;糖尿病

英文摘要： Based on the disadvantage of analytical platforms for metabonomics and the importance of diabetes research, in this project, several kinds of capillary monolithic columns were firstly prepared for the need of low-molecular metabolites including poly(MAA-co-EDMA) and organic-inorganic hybrid C8 capillary monolithic column with reverse-phase mode and poly(SPE-co-EDMA) capillary monolithic column with HILIC mode. Next, several analytical systems were developed such as HILIC-RPLC capillary liquid chromatography, on-line μE-NanoLC system and two-dimensional Ag+ LC×LC system. These platforms were then applied to the related fields such as diabetes mouse model, diabetes patients and the mechanism of TCM in treating diabetes based on metabonomics etc. Twelve significantly changed metabolites of diabetes were detected including aminomalonic acid, L-ascorbic acid and so on Berberine might play a role in the treatment of type 2 diabetes via down-regulating the high levels of free fatty acids in patient serum, thus mediating glucose and lipid metabolism. Seven papers were published and two patents were applied. Five graduate students were trained and one has graduated.

英文关键词： muti-dimensional chromatography; mass spectrometry; metabonomics; diabetes