二噁英类物质暴露与妊娠期糖尿病关系及相关microRNA差异表达研究

项目名称： 二噁英类物质暴露与妊娠期糖尿病关系及相关microRNA差异表达研究

项目编号： No.21477030

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 化学工业

项目作者： 李敬光

作者单位： 国家食品安全风险评估中心

项目金额： 90万元

中文摘要： 二噁英类物质是典型内分泌干扰物。研究显示二噁英类物质可干扰胰岛素合成、分泌和信号通路等导致胰岛素抵抗和胰岛β细胞缺陷，发生糖代谢异常。流行病学研究表明人体二噁英类物质暴露与糖代谢异常存在可能联系。孕期糖代谢异常如妊娠期糖尿病（GDM）具有较高的发病率。鉴于GDM对患者本人和子代的严重健康威胁以及会导致极大社会的负担，本研究拟开展前瞻性研究分析二噁英类物质暴露与GDM发病关系并探讨此过程中可能的表观遗传机制。研究内容包括：开发用小体积生物样本测定二噁英类物质含量方法。采用前瞻性巢式病例对照研究设计，招募GDM患者和匹配健康对照，采集血液、母乳、尿液等样本，测定其中多种化学污染物含量表征机体暴露水平，构建多元统计模型，分析二恶英类物质暴露致GDM风险，判断因果关系，检验剂量-效应关系。测定microRNAs差异表达，寻找二噁英类物质暴露致GDM效应标志物，探讨可能表观遗传学机制。

中文关键词： 持久性有机污染物；健康风险；妊娠糖尿病；微小RNA；表观遗传学

英文摘要： Dioxin-like compounds are environmental endocrine disruptors. Experimental studies have indicated that they could disrupt the insulin synthesis, secretion and signaling pathway which could lead insulin resistance and/or β-cell dysfunction, and finally, the development of abnormal glucose metabolism. Some previous epidemiological investigations have shown that there are significant relations between the abnormal glucose metabolism and exposure to Dioxin-like compounds in human being. Abnormal glucose metabolism during pregnancy, such as gestational diabetes (GDM), has relatively high incidence..GDM can pose a seroious risk to mother and child and result in huge social burden. So, to investigate the relationship between human exposure to dioxin-like compounds and GDM, a prospectively nested case-control study will be conducted in the present research. GDM patients and mathcing healthy pregnant women would be enrolled in the final study cohort, and certain biological materials, including blood and human breast milk, and population characteristics would be collected. A method will be established to accurately determine the extreme trace levels of PCDD/Fs and PCBs in small volume of human blood sample. And then, concentrations of dioxin-like compounds and some certain pollutants in these specimans would be measured to represent the level of human exposure. A multivariate model would be established to investigate the risk of the onset of GDM resulted by dioxin-like compounds exposure, and the dose-response relationship would be tested. Furthermore, the possible role of epigenetics in GDM will be investigated by examining differential expression of microRNAs from GDM patients and healthy pregnant women. Combined with the data of human exposure to dioxin-like compounds, effect biomarkers represented the relationship between the pollutants exposure and the onset of GDM would be determined, which would be useful to explore potential epigenetic pathogenic mechanism of GDM resulted by dioxin-like compounds exposure.

英文关键词： persistent orgnic pollutents;health risk;gestational dibetes mellitus;microRNA;epigenetics