Development of FIRS RNA marker in maternal plasma

母体血浆中 FIRS RNA 标记的开发

基本信息

批准号：
21591422
负责人：
SAITO Hiroshi
金额：
$ 2.91万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591422/
关键词：
胎児感染 FIRS 母体血発症予知癒着胎盤 cell-free RNA 絨毛膜羊膜炎早産予知

项目摘要

It is well known that fetal inflammatory response syndrome(FIRS) causes severe multi-organ failures in the fetus or neonate. Although premature rupture of membrane and chorioamnionitis can be developed to the FIRS, the evaluation method to diagnose the onset of FIRS has not been established. To develop the method to predict the occurrence of FIRS is therefore very important. On the other hand, we have developed the prediction method for preeclampsia by using cell-free RNA and cellular RNA in maternal blood. We planned to apply this method to the prediction of FIRS.We obtained blood samples from admitted patients with threatened preterm birth, PROM, cervicitis, and chorioamnionitis. We further obtained the data of blood counts, CRP value, elastase and fibronectin values in the cervical mucus. In cases that were performed amniocentesis, the concentrations of elastase and fibronectin were also quantified. However, in the study period, we could not obtain samples from pregnant women with fetal infection.We expect inflammatory cytokines such as interleukin-6 and interleukin-8 as molecular markers for detecting the pathogenesis of FIRS. However, the preliminary study showed that the expression levels of these markers were already altered in such situation and these candidate markers could not be used for the prediction of FIRS.Therefore, we assessed the prediction of invasive placenta by using the analysis of cellular RNA in maternal blood. The expression levels of placenta specific-1(PLAC-1) and vascular endothelial growth factor A(VEGFA) in patients with invasive placenta were higher than those in normal pregnant women. In contrast, the level of KISS-1 was lower in the patients. These genes can be potential markers to predict the abnormal adherence of the placenta.It is thus revealed that the analysis of cellular RNA in maternal blood allowed the evaluation of fetal and/or placental pathophysiological alterations.

众所周知，胎儿炎症反应综合征（FIRS）会导致胎儿或新生儿严重的多器官衰竭。虽然胎膜早破和绒毛膜羊膜炎可以发展为FIRS，但诊断FIRS发病的评估方法尚未建立。因此，开发预测FIRS发生的方法非常重要。另一方面，我们利用母血中的游离RNA和细胞RNA开发了先兆子痫的预测方法。我们计划将该方法应用于FIRS的预测。我们从入院的先兆早产、胎膜早破、宫颈炎和绒毛膜羊膜炎患者中采集了血液样本。我们进一步获得了宫颈粘液中的血细胞计数、CRP值、弹性蛋白酶和纤连蛋白值的数据。在进行羊膜穿刺术的情况下，还对弹性蛋白酶和纤连蛋白的浓度进行了定量。然而，在研究期间，我们无法获得胎儿感染孕妇的样本。我们期望白细胞介素6和白细胞介素8等炎性细胞因子能够作为检测FIRS发病机制的分子标志物。然而，初步研究表明，在这种情况下，这些标记物的表达水平已经发生改变，这些候选标记物不能用于预测FIRS。因此，我们通过分析细胞RNA来评估侵入性胎盘的预测。母血。侵袭性胎盘患者胎盘特异性1（PLAC-1）和血管内皮生长因子A（VEGFA）的表达水平高于正常孕妇。相比之下，患者中 KISS-1 的水平较低。这些基因可以作为预测胎盘异常粘附的潜在标记。因此表明，母体血液中细胞RNA的分析可以评估胎儿和/或胎盘的病理生理学改变。