Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
Alcohol. 2011 Nov;45(7):673-80. doi: 10.1016/j.alcohol.2010.11.001. Epub 2010 Dec 15.
The effects of ethanol exposure on fetal lungs remain under investigation. Previously, we demonstrated that lambs exposed to ethanol during gestation had impaired expression of pulmonary surfactant protein A, a crucial component of lung immunity. In this study, we investigated the effects of in utero exposure to ethanol on maturation and immunity of the fetal lung. Pregnant ewes were surgically implanted with an abomasal cannula and administered 1g ethanol/kg (n=8) or water (n=8) during the last trimester of pregnancy. Lambs were delivered prematurely or naturally. Neonatal lungs were assessed for maturation markers (hypoxia-inducible factor-1α [HIF-1α], HIF-2α, HIF-3α, vascular endothelial growth factor-A [VEGF-A], VEGFR-1, VEGFR-2, glycogen, and lung protein levels) and immunity (cytokines and chemokines). Preterm animals exposed to ethanol had significantly reduced VEGF-A mRNA (P=.066) and protein levels, HIF-1α (P=.055), HIF-2α (P=.019), VEGFR-1 (P=.088), and VEGFR-2 (P=.067) mRNA levels but no changes in HIF-3α mRNA. No significant changes occurred in full-term animals exposed to ethanol. Glycogen levels were significantly higher in preterm animals exposed to ethanol (P=.006) but not in full-term animals. Ethanol exposure was associated with significantly lower lung protein levels in preterm (P=.03) but not full-term animals. Preterm animals exposed to ethanol had significantly reduced TNF-α (P=.05), IL-10 (P=.03), chemokine (C-C motif) ligand 5 (CCL5) (P=.017), and monocyte chemotactic protein-1 (MCP-1) (P=.0004) mRNA. In full-term animals exposed to ethanol, the immune alterations were either sustained (TNF-α, P=.009; IL-10, P=.03) or returned to near baseline levels (CCL5 and MCP-1). The ethanol-mediated alterations in fetal lung maturation and immunity may explain the increased incidence of respiratory infections in neonates exposed to ethanol in utero.
乙醇暴露对胎儿肺部的影响仍在研究中。此前，我们证明了在妊娠期间暴露于乙醇的羔羊肺部表面活性蛋白 A 的表达受损，而该蛋白是肺免疫的关键组成部分。在这项研究中，我们研究了胎儿在子宫内暴露于乙醇对肺成熟和免疫的影响。对怀孕的母羊进行手术植入一个网胃套管，并在妊娠的最后三个月期间每天给予 1g/kg 乙醇（n=8）或水（n=8）。羔羊早产或自然分娩。对新生儿肺进行成熟标志物（缺氧诱导因子-1α[HIF-1α]、HIF-2α、HIF-3α、血管内皮生长因子-A[VEGF-A]、VEGFR-1、VEGFR-2、糖原和肺蛋白水平）和免疫（细胞因子和趋化因子）评估。暴露于乙醇的早产儿的 VEGF-A mRNA（P=.066）和蛋白水平、HIF-1α（P=.055）、HIF-2α（P=.019）、VEGFR-1（P=.088）和 VEGFR-2（P=.067）mRNA 水平显著降低，但 HIF-3α mRNA 没有变化。暴露于乙醇的足月动物没有明显变化。暴露于乙醇的早产儿的糖原水平显著升高（P=.006），但足月动物没有。暴露于乙醇的早产儿的肺蛋白水平显著降低（P=.03），但足月动物没有。暴露于乙醇的早产儿的 TNF-α（P=.05）、IL-10（P=.03）、趋化因子（C-C 基序）配体 5（CCL5）（P=.017）和单核细胞趋化蛋白-1（MCP-1）（P=.0004）mRNA 水平显著降低。在暴露于乙醇的足月动物中，免疫改变要么持续存在（TNF-α，P=.009；IL-10，P=.03），要么恢复到接近基线水平（CCL5 和 MCP-1）。乙醇对胎儿肺成熟和免疫的改变可能解释了在子宫内暴露于乙醇的新生儿呼吸道感染发生率增加的原因。
