典型镉污染地区人群样本代谢指纹图谱及健康效应指标研究

Heavy metal pollution and its health hazard are research emphasis in environment pollution and health field. The overall, dynamic and network screening of the index for toxicity evaluation is significant to investigate the poisning mechanism and conducting population healthy risk assessment. Metabonomics technology with a unitary mode can be used to integrally and thoroughly assesses the final effect of the poison to human health in complicated environment and then provides strong detection method to the screening of toxicity assessment index. The aim of this method is not limited in a single gene, protein expression and the toxic effect of abnormal single process.This study pay attention to the cadmium ion, based on large sample size population and its corresponding epidemiological survey data in typical pollution area. With a large amout of fingerprnt obtained by NMR and GC-MS or LC-MS, achieves preliminary screening of biomarkers can be received via pattern recognition technology.In order to confirm accurate and sensitive biomarkers, demonstratin is performed by large simple size population and animal experiment. From this study, an intergral, comprehensive and accurate toxic warning system is received to assessment of typical cadmium pollution area. The research provides a new idea for further development of the research about health hazards of people contaminated by cadmium and offers strong technical support for comprehensive and accurate assessment of heavy metal toxic effects.

重金属污染及其健康危害一直是环境污染与健康领域的研究重点。全面、动态、网络式筛选其毒性评价指标，对于进一步开展中毒机理和人群健康风险评价意义重大。代谢组学技术从"整体"模式出发，不局限于单一基因、蛋白的异常表达和单一毒性作用过程，整体、全面评价复杂环境中毒物对人体健康危害的最终影响，为毒性评价指标的筛选提供强有力的手段。本课题拟采用污染较为严重的镉为研究对象，以典型污染地区大量人群样本和相应流行病学资料为基础，通过核磁共振和色谱质谱联用技术获得大量样本的代谢指纹图谱，通过模式识别技术初步筛选出相应的代谢标志物，并通过动物实验加以论证，最终获得准确、敏感反映镉毒性的代谢标志物，构建一个全面评价典型镉污染地区人群健康风险的预警系统。本为进一步开展镉污染人群健康危害研究提供了新思路，为全面评价重金属污染健康危害效应提供有力的理论支持。

环境污染及其健康危害一直是众多学者关注的领域，重金属及环境雌激素则是我国典型的环境污染物。本课题选择中部某污染地区为采样点，通过收集该地区人群生物样本，运用代谢组学分析平台，检测机体内重金属镉（Cd）及邻苯二甲酸酯（PAEs）代谢物的浓度，并结合相应的流行病学资料，运用多种数据处理方法，分析影响污染物代谢的相关因素，综合评价环境污染对人群的健康效。具体而言，（1）描述了重金属镉的毒性机理及作用机制，探讨了代谢组学在毒理学中的应用。（2）运用气相质谱联用仪（GC-MS）和液相质谱联用仪（LC-MS）等代谢组学技术，检测了邻苯二甲酸酯在体内的代谢产物，分析了邻苯二甲酸酯在儿童体内的浓度，探讨了PAEs进入机体后的代谢通路。（3）运用多种代谢组学的数据处理方法，结合相应的流行病学资料，探讨了影响儿童Cd及PAEs代谢的影响因素，开展了儿童体内Cd及PAEs内暴露水平评价。（4）本课题组也同时测定了儿童血清中甲状腺相关激素及生长发育相关指标，并结合儿童体内Cd及PAEs代谢物的含量，采用多元线性回归，系统评价了环境污染物对儿童生长发育的影响。本课题为开展环境污染对人群健康危害研究提供了新的思路，为全面评价环境污染健康危害效应提供了有力的技术支持。