应用金属组学方法研究铂类抗肿瘤药物与生物体内分子的相互作用

项目名称： 应用金属组学方法研究铂类抗肿瘤药物与生物体内分子的相互作用

项目编号： No.20805048

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 王萌

作者单位： 中国科学院高能物理研究所

项目金额： 20万元

中文摘要： 金属组学是研究生命体内（细胞或器官）自由或络合的金属原子的分布、含量、化学形态及其功能的新兴学科。本课题建立和发展了适合于溶液样品和生物切片的两种分析方法，并初步应用于与金属元素有关的药物代谢、疾病机理、环境毒理等研究，希望能为金属组学研究提供的方法学支持。利用建立的HPLC/ICP-MS联用技术，研究了铂类金属药物与血清蛋白的动力学过程；建立了三价和六价铬的分析方法，分析了职业工人尿液中铬形态，提出尿液中的六价铬可以做为职业暴露的标志物；建立了稀土元素标记结合无机质谱定量分析多种蛋白质的方法，为定量蛋白质组学提供了一个很有潜力的工具。还利用同步辐射X射线荧光技术实现了生物切片中微量元素的原位成像和定量分析，并应用于分析阿尔茨海默病鼠脑中Fe、Cu、Zn等金属元素在疾病发展期间的代谢分布变化。

中文关键词： HPLC/ICP-MS；同步辐射；金属组学；金属成像

英文摘要： Metallomics is the integral study of the location, distribution, identity, species, quantity and functions of free and complex metals in biological systems, especially within a given cell or organ. Two methods are developed and applied for various metallomics study, including metallodrug metabolism, metal-related diseases, and environmental toxicity. The first method is based on HPLC/ICP-MS hyphenated techniques for solution analysis. We utilized HPLC/ICP-MS to study the reaction dynamics between bovine serum albumin and cisplatin. We also established a method for determination of Cr(III) and Cr(IV) in biological samples. The relationship analysis of urinary total Cr and urinary Cr(VI) with the airborne exposure levels suggested their feasibility to be used as monitoring indicators of the occupational exposure levels of chromate workers. At last, we worked out a method for quantitative analysis of proteins by using lanthanide labeling and ICP-MS detection, which is a promising method for quantitative proteomics. The second method is based on synchrotron radiation techniques for biological tissues. A method of in situ imaging of multi-metals in the bio-tissue slices by SR-μF was developed. The visual distributions of Ca, Fe, Cu and Zn in brain sections of AD mouse models were achieved and their alterations along with the disease development were studied.

英文关键词： HPLC/ICP-MS;synchrotron radiation; metallomics; metal imaging