微囊藻毒素低剂量暴露影响大鼠代谢组变化的核磁共振研究

项目名称： 微囊藻毒素低剂量暴露影响大鼠代谢组变化的核磁共振研究

项目编号： No.21207154

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 环境化学

项目作者： 雷和花

作者单位： 中国科学院武汉物理与数学研究所

项目金额： 24万元

中文摘要： 微囊藻毒素是富营养化水体中常见的蓝藻毒素，对环境和人类健康具有极大的危害性。流行病学调查发现多种肿瘤高发率与饮用水中微囊藻毒素污染有关。毒理学研究表明微囊藻毒素的主要靶器官是肝脏，但是其致毒机制尚不明确。申请人的前期研究结果显示微囊藻毒素能够通过血液进入机体并分布到各组织器官，势必造成体液和组织的代谢组变化。因此，本项目拟建立微囊藻毒素低剂量慢性暴露的动物模型，应用基于核磁共振技术的代谢组学方法研究微囊藻毒素的毒性效应。通过分析微囊藻毒素暴露前后大鼠尿液、血浆及肝脏等组织代谢物组成的变化，可以找到大鼠的内源性代谢对毒素暴露所产生的应答反应规律，发现毒素影响的代谢标志物，为阐明微囊藻毒素的致毒机制提供基础信息，同时为确定微囊藻毒素的安全限值和采取防治措施提供科学依据。本项目将先进的代谢组学技术应用于环境污染物和人类健康问题的研究，为环境污染物对人类健康影响的监测、预防及治疗提供新的思路。

中文关键词： 微囊藻毒素；低剂量暴露；代谢组学；核磁共振；

英文摘要： Microcystins (MCs) are common cyanobacterial toxins in eutrophicated water body and have caused serious damage to both environment and human health.Epidemiological surveys showed that high incidence of cancer cases were associated with MCs contamination in drinking water. Previous toxicological studies indicated that the target organ of MCs is liver. Toxic mechanism of MCs still remains unclear. The applicant's preliminary study showed MCs can enter into the circulatory system and be transported to various organs. This is bound to change the metabonome of body fluids and tissues. So in this project, we will develop an animal model to study chronic toxic effects of low dose MC, employing Nuclear Magnetic Resonance (NMR) - based metabonomic strategy. This project is expected to find the changes' rules of endogenous metabolism and the biomarkers in rat response to MC exposure, by analyzing metabolic changes in rat urine, plasma and tissues before and after exposure. The results will provide basic information for understanding the toxic mechanism of MC and further provide scientific evidences for the prevention and treatment of MC poisoning. In this project, we employ advanced metabonomic strategy to study the linkages between environmental pollutants and health. This expands new pathway for monitoring, prevention a

英文关键词： microcystin；low dose exposure；metabonomics；NMR；