Allison Beth J, Hooper Stuart B, Coia Elise, Zahra Valerie A, Jenkin Graham, Malhotra Atul, Sehgal Arvind, Kluckow Martin, Gill Andrew W, Sozo Foula, Miller Suzanne L, Polglase Graeme R
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia;
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia;
Am J Physiol Lung Cell Mol Physiol. 2016 Feb 1;310(3):L213-23. doi: 10.1152/ajplung.00328.2015. Epub 2015 Nov 25.
Intrauterine growth restriction (IUGR) and preterm birth are frequent comorbidities and, combined, increase the risk of adverse respiratory outcomes compared with that in appropriately grown (AG) infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared with AG infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements, and/or increased ventilation-induced lung injury. IUGR was surgically induced in preterm fetal sheep (0.7 gestation) by ligation of a single umbilical artery. Four weeks later, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Ventilator requirements, lung inflammation, early markers of lung injury, and morphological changes in lung parenchymal and vascular structure and surfactant composition were analyzed. IUGR preterm lambs weighed 30% less than AG preterm lambs, with increased brain-to-body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared with AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth and had significant, but similar, increases in proinflammatory cytokine expression, lung injury markers, gene expression, and surfactant phosphatidylcholine species compared with unventilated controls. IUGR does not induce pulmonary structural changes in our model. Furthermore, IUGR and AG preterm lambs have similar ventilator requirements in the immediate postnatal period. This study suggests that increased morbidity and mortality in IUGR infants is not due to altered lung tissue or vascular structure, or to an altered response to early ventilation.
宫内生长受限(IUGR)和早产是常见的合并症,与生长正常(AG)的婴儿相比,二者共同增加了不良呼吸结局的风险。与AG婴儿相比,IUGR婴儿呼吸发病率增加的潜在根本原因包括胎儿肺发育改变、胎儿肺部炎症、呼吸需求增加和/或通气诱导的肺损伤增加。通过结扎单根脐动脉,在早产胎羊(妊娠0.7期)中手术诱导IUGR。四周后,早产羔羊在分娩时安乐死,或分娩后通气2小时再安乐死。分析了通气需求、肺部炎症、肺损伤早期标志物以及肺实质和血管结构及表面活性剂成分的形态学变化。IUGR早产羔羊的体重比AG早产羔羊轻30%,脑体比增加,表明存在脑保护现象。与AG胎儿相比,IUGR并未诱导肺部炎症或损伤,也未改变肺实质和血管结构。IUGR羔羊和AG羔羊出生后的氧合和呼吸需求相似,与未通气的对照组相比,促炎细胞因子表达、肺损伤标志物、基因表达和表面活性剂磷脂酰胆碱种类均有显著但相似的增加。在我们的模型中,IUGR不会诱导肺部结构变化。此外,IUGR早产羔羊和AG早产羔羊在出生后即刻的通气需求相似。这项研究表明,IUGR婴儿发病率和死亡率增加并非由于肺组织或血管结构改变,也不是由于对早期通气的反应改变。