中文摘要
胎儿是大气细颗粒物(PM2.5)的易受伤害群体,其心血管系统是PM2.5不良效应的主要作用系统,但目前针对出生前PM2.5及其毒性成分暴露对胎儿心血管发育的不良效应及其作用机制的研究报道很少。项目制备并分析本地区PM2.5及其毒性组分多环芳烃(PAHs)样本,在大鼠出生前PM2.5或PAHs暴露模型上,观察标准允许浓度、高浓度PM2.5或PAHs暴露对胎鼠心血管发育的影响,探讨其作用机制。通过临床研究观察不同类型胎儿心血管畸形病例心血管发育敏感指标的变化,分析其与PM2.5暴露水平的关联性以与实验研究结果互为印证,阐释PM2.5暴露-心血管发育调控异常-心血管畸形发生的内在联系。该研究将明确出生前PM2.5及其主要毒性成分暴露对心血管发育的不良效应,阐释其作用机制,为大气污染治理的规划目标和力度、大气污染允许标准对胎儿发育的安全性提供判定依据,并为妊娠期母婴保健和优生优育施政提供重要参考。
英文摘要
Fetus is regarded as one of the most vulnerable subjects, and cardiovascular system as one of the most susceptible systems with regard to airborne fine particulate matter (PM2.5) exposure. It is, therefore, extraordinarily necessary to understand the potential toxic effects of exposure to high or cirteria levels of PM2.5 or its major venenous components, on fetal cardiovascular system. However, there have been rare experimental research reports on this issue. In the present applying project, samples of the local PM2.5 and its derivative polycylic aromatic hydrocarbons (PAHs) will be prepared with their major toxic components analyzed. The effects of prenatal exposure to high levels or criteria levels of PM2.5, or its major toxic conponent PAHs, on fetal cardiovascular development will be experimentally investigated in murine exposure models via intratracheal instillation of the resuspended PM2.5 or resolved PAHs, or via inhalation of local PM2.5 at the ambient levels. The mechanisms by which prenatal PM2.5 or PAHs exposure acts on fetal cardiovascular system will be explored. In the clinical study, the sensitive indicators for fetal cardiavascular development in relation to prenatal exposure to PM2.5 will be investigated in the fetuses with different subtypes of congenital heart diseases to further prove the results from the experimental studies and to uncover the underlying relevance of PM2.5 exposure-regulatory abnormality-cardiovascular anomalies. By providing the epidemiological and experimental evidences for the relationship between PM2.5, its major components PAHs and fetal cardiovascular malformations, the present work will offer an important base for understanding the negative impacts of PM2.5 or its components on fetal cardiovascular development and their underlying mechanisms. The work will provide, more importantly, evidences and references to the environmental agency and governments for a validation of the currently revised criteria in the Chinese ambient pollutant standards, a gross planning objective and the necessity and strength of finance and power for comprehensive management of air pollution. It is also pivotal to birth defect monitoring & control and to maternal and infant care.
