多环芳烃诱发自发性早产的效应与机制以及叶酸的保护作用

随着我国多环芳烃（PAHs）污染的加剧，其对妊娠结局的影响备受关注。有研究提示，PAHs可诱发早产，炎性反应可能是其重要机制。本研究采用孕期队列及队列内病例对照研究、结合大鼠模型揭示孕期PAHs暴露对自发性早产（SPB）的诱发效应、炎性反应在其中的作用及叶酸拮抗PAHs诱发SPB的效应。拟在北京市城区（室外大气污染为主）和山西农村地区（室内空气污染为主）各募集约3000名孕20周之前的妇女，收集孕早、中期PAHs暴露及叶酸服用相关信息，采集妇女静脉血保存，随访妇女妊娠结局。从两个队列中各选择SPB病例及配比对照120对（共480名），测定血清PAHs浓度、相关代谢酶基因多态性及炎性因子水平。分析队列人群PAHs暴露及叶酸服用情况及病例对照人群各标志物与SPB的关系。通过构建大鼠PAHs染毒及叶酸干预模型，直观验证PAHs诱发SPB的效应和分子机制，以及叶酸对PAHs诱发SPB的保护作用。

The effects of polycyclic aromatic hydrocarbons (PAHs) exposure on pregnancy outcomes are concerned greatly with its exposure increasing in our country. Emerging evidence suggested that PAHs exposure may result in preterm births, inflammatory response may play an important role, while folic acid may have an anti-inflamatory effect and prevent against preterm births. We propose to conduct a pregnancy cohort study and nested case-control study, combined with rat experiment to examine the association of maternal PAHs exposure during pregnancy with spontaneous preterm birth(SPB), the role of inflamatory response and the preventive effect of folic acid on SPB. About 3000 pregnant women will be recruited before 20 weeks gestation in Beijing urban area (mainly ourdoor air pollution) and Shanxi rural area (mainly indoor air pollution), respectively. Information related to PAHs exposure during first and second trimester and folic acid use will be investigted, and women’s venous blood samples will be collected during the recruitment. The recruited women will be followed to verify the pregnancy outcomes. In each cohort, 120 women with spontaneous preterm births and 120 matched controls will be selected respectively (480 subjects in total) for measurement of serum PAHs, inflammatory cytokines, as well as related gene polymorphisms. The associations of PAHs exposure and folic acid use in cohort study and the level of various biomarkers in nested case control study with preterm birth with be analyzed. Rat models of PAHs exposure and folic acid intervention will be established to directly observe the effects of PAHs on SPB and the molecular mechanisms by which PAHs may result in SPB, as well as protective effect of folic acid against PAHs-induced SPB.