生命早期二噁英类化合物暴露通过慢性炎症增加糖尿病易感性的研究

生命早期化学污染物暴露可增加成年期慢性代谢性疾病发生风险。我们前期研究发现电子垃圾污染区人体二噁英类化合物（DLCs: PCDDs、PCDFs、DL-PCBs）含量高于其它地区，使人体处于慢性炎症前期；动物实验证明慢性炎症与慢性代谢性疾病如糖尿病有关。我们推测生命早期DLCs可通过胎盘屏障进入子代，诱发慢性炎症，慢性炎症一方面可造成胰岛素耐受，另一方面也可导致胎儿糖尿病易感基因和糖代谢相关基因甲基化水平发生变化，增加糖尿病易感性。为验证以上科学假设，本项目将通过采集母体（静脉血、尿液）和新生儿样本（脐带血、胎盘和脐带），检测DLCs在人体蓄积水平，分析DLCs水平、炎症指标（炎症介质、产妇体温和血常规）与糖尿病相关基因的交互作用，及其对血糖、胰岛素、脂质代谢物等的影响，揭示生命早期DLCs暴露通过炎症通路，增加糖尿病易感性的分子机制和表观遗传效应，为糖尿病的早期筛查和预测预警提供科学依据。

Early life exposure to chemical contaminants increases the risk of chronic metabolic diseases in adulthood. Our previous studies have found that the body burden of dioxin-like compounds (DLCs), such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (DL-PCBs), in residents from the electronic waste (e-waste) recycling area are higher than these in other areas, and lead to the prophase of chronic inflammation. Animal experiments have proved that chronic inflammation is associated with some chronic metabolic diseases, such as diabetes. We speculate that DLCs in early life can enter the offspring through the placental barrier and cause a chronic inflammatory status, which further result in insulin resistance as well as methylation changes in diabetes susceptibility genes and glycometabolism-related genes, finally increasing the diabetes susceptibility in adulthood. To verify the above scientific hypothesis, the accumulation of DLCs in human samples including maternal (venous blood and urine) and neonatal (cord blood, placenta and umbilical cord) samples will be detected, and the interaction between DLC levels and inflammatory indicators (inflammatory mediators, maternity body temperature, blood routine examination) as well as the alterations of diabetes-related genes, glycometabolism-related genes, blood glucose and insulin will be analyzed. We hope to demonstrate the impacts of early-life exposure to DLCs on the methylation status and transcriptional level of diabetes-related genes, and to illuminate the underlying molecular mechanisms and epigenetics of increasing the diabetes susceptibility via inflammatory pathways, and to provide scientific basis for early screening and prediction of diabetes.