生命早期PFOS替代品暴露致神经发育毒性的影响及其机制研究

Perfluorooctane sulfonate (PFOS) is a man-made perfluorocarbons (PFCs) and global pollutant. It is an exceptionally stable compound in industrial applications and in the environment because of the effect of aggregate carbon-fluorine bonds. Health concerns for PFOS include hepatotoxicity, developmental toxicity, immunotoxicity, hormone disturbances, and tumorigenic potential. As a result, PFOS has been forbidden in Europe and America which places China the largest PFOS producer in the world. It’s crucial for China to find a suitable alternative chemical of PFOS. However, the long-term effects of potential alternatives (perfluorohexanesulfonate, PFHS and Perfluorobutanesulfonic acid PFBS) on human health remain unknown. Some animal research suggests that PFOS may increase the risk of mental retardation. In this study, we propose to conduct a prospective cohort study to examine the association between PFOS alternatives and child neurobehavioral development in Shanghai Birth Cohort. We will further explore plausible biological mechanisms in neuron culture to compare the effect of each kind of PFCs on neuron plasticity, and the role of microRNA in this association. This study will take advantage of an on-going large prospective cohort study to examine the long-term effects of PFCs on child health, and to provide evidence for sound health policy.

全氟辛烷磺酸（PFOS)应用广泛，但降解性低、毒性大。我国是世界上最大的PFOS生产国，寻找PFOS的替代品迫在眉睫。全氟己烷磺酸盐（PFHS）和全氟丁烷磺酸盐(PFBS) 是PFOS潜在替代品，然而其对人体远期健康风险无可靠证据。尽管动物实验表明PFOS可致神经发育毒性，孕期PFOS替代品暴露对儿童神经行为的影响从未明确。我们已建立了PFCs检测方法，本研究将在已开展的上海出生队列平台上进行前瞻性研究，定量评价生命早期PFOS及替代品对神经行为发育的影响。同时，在预实验基础上，利用已建立的大脑皮层神经元染毒模型，比较PFOS及其替代品对神经元突触可塑性毒性的强弱，探索miR-132介导的PFCs对神经元可塑性相关蛋白表达的调节作用。在广泛使用的PFOS即将被禁用的关键时期，合理评估PFOS替代品对人体的安全性具有重大意义。本研究有利于早期预防提高人群健康，也为政府提供依据。

尽管动物实验表明PFOS可致神经发育毒性，孕期PFOS替代品暴露对儿童神经行为的影响从未明确。本研究获得了上海市孕期全氟化合物（PFCS）包括PFOS及其同类的暴露水平，发现PFOA上海市最高水平。系统分析了孕期的的潜在替代品对儿童多系统远期健康风险，发现低浓度的 PFOS 及其他全氟类化合物对儿童的远期智力发育没有影响。人群部分较原计划超额完成，除了 PFOS，额外完成了 12 种全氟化合物对人体的其他影响及其分子流行病学机理。本研究发现，PFCS与儿童肥胖存在关联，尤其PFBS最为密切。与多种肝脏功能指标存在关联，维生素D可能解救其带来的损伤。我们将进一步开展PFCS对儿童健康影响的机制研究。

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