Intra-amniotic endotoxin: chorioamnionitis precedes lung maturation in preterm lambs

Intra-amniotic endotoxin: chorioamnionitis precedes lung maturation in preterm lambs
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DOI:
10.1152/ajplung.2001.280.3.l527
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发表时间:
2001-03-01
影响因子:
4.9
通讯作者:
Bachurski, CJ
Bachurski, CJ
中科院分区:
医学2区
文献类型:
--
作者:
Kallapur, SG;Willet, KE;Bachurski, CJ

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在胎羊中评估羊膜内暴露于内毒素的炎症和肺成熟效应。羊膜腔内注射内毒素后5小时至25天,早产羔羊在妊娠119-125天分娩。羊膜内毒素作用5 h后,羊膜/绒毛膜出现炎性细胞浸润,持续25 d。内毒素后5-15 h,羊膜/绒毛膜细胞因子mRNA增加[白细胞介素(IL)-1 β、IL-6和IL-8 mRNA增加12- 26倍,肿瘤坏死因子-α mRNA增加3倍]。在内毒素后1-2天,肺细胞因子mRNA增加6- 49倍。内毒素引起外周白色血细胞计数的适度变化,胎肝、胎盘或空肠中无显著细胞因子mRNA反应。肺成熟,其特征是增加肺容量和肺泡饱和磷脂酰胆碱,发生在7天,并持续25天后内毒素。我们的结论是,暴露于单一剂量的羊膜内毒素导致炎症和细胞因子mRNA在羊膜/绒毛膜和肺成熟前的胎肺中的增加,与促炎细胞因子信号肺成熟的假设一致。
The inflammatory and lung maturational effects of intra-amniotic exposure to endotoxin were assessed in fetal lambs. Five hours to 25 days after intraamniotic injection of endotoxin, preterm lambs were delivered at 119-125 days gestation. Intra-amniotic endotoxin caused an inflammatory cell infiltration in amnion/chorion at 5 h, which persisted for 25 days. At 5-15 h after endotoxin, amnion/chorion cytokine mRNAs increased [12- to 26-fold for interleukin (IL)-1 beta, IL-6, and IL-8 mRNA and 3-fold for tumor necrosis factor-alpha mRNA]. At 1-2 days after endotoxin, lung cytokine mRNAs increased 6- to 49-fold. Endotoxin caused modest changes in peripheral white blood cell counts and no significant cytokine mRNA responses in fetal liver, placenta, or jejunum. Lung maturation, as characterized by increased lung volumes and alveolar saturated phosphatidylcholine, occurred at 7 days and persisted for 25 days after endotoxin. We conclude that exposure to a single dose of intra-amniotic endotoxin causes inflammation and increases in cytokine mRNA in amnion/chorion and the fetal lung before lung maturation, consistent with the hypothesis that proinflammatory cytokines signal lung maturation.