妊娠期磷脂-花生四烯酸代谢网络变化及其诱导分娩启动的队列研究

Initiation of parturition is critical to the prevention of adverse birth outcomes, however, it is still a difficult problem of public health research. The present study will focus on the hypothesis that the phospholipid-arachidonic acid metabolic network is closely related to the initiation of parturition. The LC-QTOF-MS/MS and LC-QTRAP-MS/MS will be integrated to establish a targeted characteristic profile, which can enable the qualitative and quantitative analysis of the phospholipid-arachidonic acid metabolic network on the basis of the established very large pregnant cohort. The status of phospholipid-arachidonic acid metabolic network in early, middle, and late pregnancy stages will be monitored by the use of established method. Then the varieties of key target and trajectory of pregnancy network will be clarified by the comparison of qualitative and quantitative analysis of pregnancy network in three different periods. Finally, the correlation analysis will be conducted between the index of the initiation of parturition and the varieties of key target to screen the biomarkers that can early predict the initiation of parturition. The project first give the evidence of a connection between the phospholipid-arachidonic acid metabolic network and initiation of parturition based on a very large pregnant cohort. The results can also provide a guidance and a theoretical basis for the established of strategies on the early prevention and intervention of adverse birth outcomes from molecular levels.

妊娠分娩启动的早期预测是全球公共卫生的研究难题，它对不良出生结局的预防至关重要。本项目紧密围绕提出的假说：磷脂-花生四烯酸代谢网络与妊娠分娩启动密切相关，在已建立的大型出生队列基础上，整合应用高分辨LC-QTOF-MS/MS和高灵敏LC-QTRAP-MS/MS两种功能的质谱，构建磷脂-花生四烯酸代谢网络的LC-QTOF-MRM靶标性特征谱分析方法；通过靶向跟踪研究妊娠早、中、晚三期的磷脂-花生四烯酸代谢网络状态，比较不同妊娠期网络成分的种类和含量差异，揭示妊娠期网络关键变化靶点和轨迹；进而将队列人群分娩启动指标和关键变化靶点进行关联分析，明确磷脂-花生四烯酸代谢网络变化与分娩启动的关系，最终筛选能够有效早期预测分娩启动的生物标志物。本项目将磷脂-花生四烯酸代谢网络与分娩启动的预测有机联系起来，研究立足于大型孕妇队列，可为不良出生结局的早期预防和干预策略提供指导和分子水平的理论依据。

妊娠分娩启动的早期预测对不良出生结局的预防至关重要，本项目紧密围绕科学假说：磷脂-花生四烯酸代谢网络与妊娠分娩启动密切相关，在已建立的大型出生队列基础上，（1）利用LC-MS/MS构建磷脂-花生四烯酸代谢网络的靶标性特征谱分析方法，最终构建孕妇血清代谢网络数据库，包括656种磷脂类成分和119种花生四烯酸代谢产物；（2）利用靶向代谢组学方法跟踪研究妊娠期的磷脂-花生四烯酸代谢网络状态，比较不同妊娠期网络成分的种类和含量差异，初步发现有107种化合物与妊娠期显著相关；（3）再将队列人群分娩启动指标和关键变化靶点进行关联分析，明确磷脂-花生四烯酸代谢网络变化与分娩启动的关系，进一步确认52种化合物与分娩启动密切关联；（4）综合校正人群影响因素，最终筛选出25个能有效早期预测分娩启动的生物标志物。本项目将磷脂-花生四烯酸代谢网络与分娩启动的预测有机联系起来，研究立足于大型孕妇队列，可为不良出生结局的早期预防和干预策略提供指导和分子水平的理论依据，生物标志物的发现可为妊娠分娩启动提供更准确的参考。