广州市PM2.5机动车来源成分与早产的关系及LINE-1基因甲基化机制研究

Preterm birth is the leading cause of perinatal mortality, and its causes are very complicated. The association of ambient fine particulate matter (PM2.5) with preterm have been emphasized in recent many studies. One of our recent studies also observed significantly positive relationships between pregnant PM2.5 exposure concentrations and preterm risk. However, PM2.5 has very complex components, and the harm effects of its different components might largely differentiate. Vehicle emissions are important sources of PM2.5 in the urban areas. Their effects on preterm risks remain unclear, and the biological mechanisms of these effects are still unclear. It was hypothesized that LINE-1 methylation may be an important biomarker. Based on previous study findings, we hypothesize that pregnant PM2.5 exposure might suppress LINE-1 methylation level, which could up-regulate the expressions of this gene and hence increase the inflammatory reactions that might subsequently trigger the fetal birth process in advance. In this study, we plan to conduct a hospital based cohort study in Guangzhou, in which we will choose early pregnant women and follow up them till to their fetal births. Each participant will be interviewed with a standard questionnaire, and be collected blood samples. Individual level PM2.5 exposure during the early, middle and late pregnancy will be assessed by a new particulate exposure evaluation model. All these data will be used to assess the associations of vehicle sourced PM2.5 chemical components with preterm birth. On the basis of this cohort study, a nested case-control study will be conducted, in which preterm cases and controls will be selected, and their LINE-1 methylation levels will be tested. We aim to demonstrate the moderation effect of LINE-1 methylation changing in the process of PM2.5 exposure leading to preterm birth. These results could provide scientific evidence for the local governments and policy makers to make air pollution controlling specific measures.

早产是新生儿死亡的首要原因，其病因复杂。细颗粒物(PM2.5)的影响日趋受关注，我们前期研究也发现孕期PM2.5暴露可增加早产风险，然而PM2.5成分复杂，不同成分的危害不同。机动车日益成为城市PM2.5的重要来源，其与早产的关系如何尚待明确，且其生物学机制尚不清楚，有研究提示LINE-1甲基化改变可能是重要环节。我们提出如下假设：PM2.5可通过降低LINE-1甲基化水平而上调基因表达，进而激活炎性反应，提前启动分娩。我们拟在广州开展队列研究，基于医院选择孕早期孕妇进行随访，收集信息和血样，采用颗粒物暴露评价模型评估每个孕妇不同孕期的PM2.5暴露量，旨在明确孕期PM2.5机动车源成分暴露与早产的关系。进一步开展巢式病例对照研究选择早产和对照，检测LINE-1甲基化水平，阐明LINE-1甲基化改变在PM2.5机动车源成分引起早产中的作用机制。为政府采取针对性措施控制空气污染提供科学依据

早产是新生儿死亡的首要原因，其病因复杂。空气污染日趋严重，许多研究关注空气颗粒物污染中PM2.5和PM10对早产的影响，缺乏综合分析不同粒径颗粒污染物与早产的关系的研究。而且，PM2.5成分复杂，不同成分的危害不同，其与早产的关系如何尚待明确。空气颗粒污染物影响早产的生物学机制尚不明确，有研究提示LINE-1甲基化改变可能是重要环节。据此，本研究在广州开展队列研究，旨在明确孕期空气粒径颗粒污染物暴露和PM2.5成分暴露与早产的关系，并探讨LINE-1基因甲基化在孕期大气颗粒污染物浓度暴露引起早产中的作用机制。本研究发现，孕期大气颗粒污染物的暴露可增加早产发生的风险，粒径越小，早产发生的风险越大。暴露敏感期为孕早期和孕中期（第12-20周）。孕期暴露于Cl、锑、镉、铬、铅等成分者发生早产的风险较高，同时，孕期大气颗粒污染物暴露对孕妇血和脐带血中LINE-1甲基化水平呈负相关，且孕妇血中LINE-1甲基化水平与早产呈负关联，脐带血中LINE-1甲基化水平与早产呈正关联。综上，本研究进一步明确了大气颗粒污染物及不同成分对早产的影响，并明确了暴露敏感期，LINE-1甲基化改变可能是在孕期大气颗粒污染物浓度暴露引起早产的重要机制。