Vitamin D treatment improves survival and infant lung structure after intra-amniotic endotoxin exposure in rats: potential role for the prevention of bronchopulmonary dysplasia
Vitamin D treatment improves survival and infant lung structure after intra-amniotic endotoxin exposure in rats: potential role for the prevention of bronchopulmonary dysplasia
复制标题
DOI：
10.1152/ajplung.00344.2013
复制
发表时间：
2014-03-01
影响因子：
4.9
通讯作者：
Abman, Steven H.
中科院分区：
文献类型：
--
作者：
Mandell, Erica;Seedorf, Gregory;Abman, Steven H.
维生素D （vit D）具有抗炎特性并调节肺生长，但维生素D是否可以预防暴露于产前炎症后的肺损伤尚不清楚。我们假设早期和持续的vit D治疗可以提高胎儿暴露于内毒素（ETX）诱导的支气管肺发育不良实验模型的生存率并保持肺生长。将胎鼠（E20）通过羊膜内（IA）注射ETX （10 μ g）、ETX + Vit D （1 ng/ml）或生理盐水（对照），并于2天后分娩。暴露于IA ETX的新生幼崽每天腹腔注射维生素D （1 ng/g）或生理盐水，持续14天。与单独使用IA ETX相比，Vit D治疗改善了IA ETX暴露后的血氧饱和度（78%对87%，P < 0.001）和产后生存率（84%对57%，P < 0.001）。产后vd治疗可使第14天肺泡和血管生长分别提高45%和25% （P < 0.05）。Vit D可使胎羊肺动脉内皮细胞（PAEC）生长和成管率分别提高64%和44% (P < 0.001)，并能抑制etx诱导的PAEC生长和成管率的降低。Vit D直接使胎儿肺泡II型细胞（ATIIC）的生长增加26% (P < 0.001)，在etx诱导的生长抑制下，ATIIC的生长增加了73% （P < 0.001）。我们得出结论，产前维生素D治疗改善了新生大鼠幼崽体内暴露于IA ETX后的氧合和存活，并增强了晚期肺结构，这可能部分是由于对血管和肺泡生长的直接影响。
Vitamin D (vit D) has anti-inflammatory properties and modulates lung growth, but whether vit D can prevent lung injury after exposure to antenatal inflammation is unknown. We hypothesized that early and sustained vit D treatment could improve survival and preserve lung growth in an experimental model of bronchopulmonary dysplasia induced by antenatal exposure to endotoxin (ETX). Fetal rats (E20) were exposed to ETX (10 mu g), ETX + Vit D (1 ng/ml), or saline (control) via intra-amniotic (IA) injections and delivered 2 days later. Newborn pups exposed to IA ETX received daily intraperitoneal injections of vit D (1 ng/g) or saline for 14 days. Vit D treatment improved oxygen saturations (78 vs. 87%; P < 0.001) and postnatal survival (84% vs. 57%; P < 0.001) after exposure to IA ETX compared with IA ETX alone. Postnatal vit D treatment improved alveolar and vascular growth at 14 days by 45% and 25%, respectively (P < 0.05). Vit D increased fetal sheep pulmonary artery endothelial cell (PAEC) growth and tube formation by 64% and 44%, respectively (P < 0.001), and prevented ETX-induced reductions of PAEC growth and tube formation. Vit D directly increased fetal alveolar type II cell (ATIIC) growth by 26% (P < 0.001) and enhanced ATIIC growth in the presence of ETX-induced growth suppression by 73% (P < 0.001). We conclude that antenatal vit D therapy improved oxygenation and survival in newborn rat pups and enhanced late lung structure after exposure to IA ETX in vivo, which may partly be due to direct effects on vascular and alveolar growth.