大鼠胎儿窒息预处理导致出生时胎盘炎症表型得以保留。

Fetal asphyctic preconditioning in rats results in a preserved placental inflammatory phenotype at birth.

作者信息

Sparnaaij Michelle, Chedraui Peter, Liem Kim H, Escobar Gustavo S, Espinoza-Caicedo Jasson, Kramer Boris W, Vles Johan S H, Gavilanes Antonio W D

机构信息

Department of Pediatrics - Division of Neonatology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Neuropsychology - Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, The Netherlands; Child Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.

Institute of Biomedicine, Faculty of Medicine, Catholic University of Santiago de Guayaquil, Guayaquil, Ecuador; Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil, Ecuador.

出版信息

Placenta. 2016 Feb;38:84-92. doi: 10.1016/j.placenta.2015.12.016. Epub 2015 Dec 24.

DOI:10.1016/j.placenta.2015.12.016

PMID:26907386

Abstract

INTRODUCTION

Perinatal asphyxia (PA) is a major cause of neonatal mortality and morbidity. Research has shown that in rats fetal asphyxia (FA) can provoke neuroprotection against a subsequent more severe perinatal asphyctic insult. This is called fetal asphyctic preconditioning (PC). Our objective was to investigate alterations in the placental inflammatory phenotype associated with PC.

METHODS

FA was induced in the rat at embryonic day 17 by reversibly clamping the uterine circulation and PA was induced at birth by submersion of the uterine horns in a saline bath for 19 min. The effect of PC was studied by inducing FA at E17, followed by PA at E21. Placental TNF-α, IL-1β, IL-6 and IL-10 mRNA and protein levels were measured by qPCR and ELISA.

RESULTS

IL-1β mRNA increased in the labouring FA group, but IL-1β protein decreased after both FA and PA. In the PC group, IL-1β mRNA and protein levels were similar to controls. IL-6 protein increased 6 h after FA, however decreased 24 h after FA. IL-6 mRNA was higher in the labouring PA group. IL-10 protein decreased 24 h after FA. At birth, IL-10 mRNA increased in the PA group; however, IL-10 protein decreased in both the PA and the FA group. In the PC group, IL-10 mRNA and protein were similar to control levels.

DISCUSSION

Depleted protein concentrations of IL-10 and IL-1β after one single asphyctic insult were reversed after fetal asphyctic PC. In addition, PC placentas showed less up-regulation of IL-6 mRNA compared to the PA ones. This modulated placental inflammatory phenotype might contribute to the improved neonatal outcome showed after fetal asphyctic PC.

摘要

引言

围产期窒息（PA）是新生儿死亡和发病的主要原因。研究表明，在大鼠中，胎儿窒息（FA）可引发对随后更严重围产期窒息性损伤的神经保护作用。这被称为胎儿窒息预处理（PC）。我们的目的是研究与PC相关的胎盘炎症表型的变化。

方法

在胚胎第17天通过可逆性夹闭子宫循环诱导大鼠发生FA，并在出生时通过将子宫角浸入盐水中19分钟诱导PA。通过在E17诱导FA，然后在E21诱导PA来研究PC的作用。通过qPCR和ELISA测量胎盘TNF-α、IL-1β、IL-6和IL-10 mRNA及蛋白水平。

结果

分娩期FA组中IL-1β mRNA增加，但FA和PA后IL-1β蛋白均减少。在PC组中，IL-1β mRNA和蛋白水平与对照组相似。FA后6小时IL-6蛋白增加，但FA后24小时减少。分娩期PA组中IL-6 mRNA更高。FA后24小时IL-10蛋白减少。出生时，PA组中IL-10 mRNA增加；然而，PA组和FA组中IL-10蛋白均减少。在PC组中，IL-10 mRNA和蛋白与对照水平相似。