混合型高分辨质谱联用解析CADs代谢谱及对恶性肿瘤协同干预作用机制

项目名称： 混合型高分辨质谱联用解析CADs代谢谱及对恶性肿瘤协同干预作用机制

项目编号： No.81473020

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李磊

作者单位： 南京医科大学

项目金额： 80万元

中文摘要： 咖啡酸衍生物（CADs）广泛存在于果蔬及蜂蜜等食品中。流行病学调查表明，经常食用CADs可预防恶性肿瘤发生。但跟踪研究发现，CADs生物活性的体内、体外实验结果有较大差异，多种CADs代谢表达与抗肿瘤活性的关联性尚不清楚。本项目基于代谢组学方法和超高效液相色谱-四极杆-静电场轨道阱高分辨混合质谱手段，探索CADs代谢uHPLC-ESI-MS-MS指纹图谱构建及表征方法，以发现CADs代谢组分和代谢指纹区；基于uHPLC-DPPH-DAD/ESI-MS-MS-uCL联用技术评价CADs代谢指纹区对DNA链断裂的协同抑制作用，以发现CADs可能的抗肿瘤活性成分；解析CADs/代谢标志物对恶性肿瘤代谢差异表达的影响，以探明CADs及指纹区抗癌作用途径；开展细胞学和荷瘤动物实验，以观察CADs代谢标志物对恶性肿瘤的协同干预效应及机制。为恶性肿瘤膳食干预研究提供卫生分析新原理、新方法。

中文关键词： 咖啡酸衍生物；代谢谱；联用技术；恶性肿瘤；协同干预

英文摘要： Caffeic Acid Derivatives（CADs）were widely spread in food such as fruits, vegetables and honey, etc. Epidemiological surveys showed that regular consumption of CADs could prevent the occurrence of malignant tumor. But a series of follow-up study found that the CADs' bioactivities in vivo and in vitro studies had bigger difference. It's necessary to carry out correlation analysis between multi-CADs metabolic expression and their anti-tumor activities. This project was to establish CADs metabolic uHPLC-ESI-MS-MS fingerprinting and expression method to find CADs metabolic components, metabolic fingerprint region and the growth trend based on metabonomics method and hyphenated technology, a ultra-high performance liquid chromatography (uHPLC) -quadrupole-electrostatic field orbit trap high resolution tandem mass spectrum, chemical metrology analysis coupling organism model. It was used to evaluate the joint protection of CADs metabolic fingerprint region on DNA strand breakage to detect possible CADs antitumor active ingredient based on uHPLC-DPPH-DAD/ESI-MS-MS-uCL hyphenated detection. The influence of CADs and its metabolic marker on malignant tumor metabolic differentially expressed was deep to prove possible metabolic and anticancer pathway. The cytology and tumor-burdened bone in vivo animal experiment was employed to observe synergistic intervention action and molecular mechanism of CADs metabolic markers on anticancer. A new principle and new method was proposed for further research on malignant tumor of dietary intervention.

英文关键词： Caffeic acid derivatives;metabolite profiling;hyphenated technology;malignant tumor;synergistic intervention