Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Ohio 45229-3039, USA.
Am J Physiol Lung Cell Mol Physiol. 2011 Feb;300(2):L232-41. doi: 10.1152/ajplung.00294.2010. Epub 2010 Dec 3.
Mechanical ventilation is a risk factor for the development of bronchopulmonary dysplasia in premature infants. Fifteen minutes of high tidal volume (V(T)) ventilation induces inflammatory cytokine expression in small airways and lung parenchyma within 3 h. Our objective was to describe the temporal progression of cytokine and maturation responses to lung injury in fetal sheep exposed to a defined 15-min stretch injury. After maternal anesthesia and hysterotomy, 129-day gestation fetal lambs (n = 7-8/group) had the head and chest exteriorized. Each fetus was intubated, and airway fluid was gently removed. While placental support was maintained, the fetus received ventilation with an escalating V(T) to 15 ml/kg without positive end-expiratory pressure (PEEP) for 15 min using heated, humidified 100% nitrogen. The fetus was then returned to the uterus for 1, 6, or 24 h. Control lambs received a PEEP of 2 cmH(2)O for 15 min. Tissue samples from the lung and systemic organs were evaluated. Stretch injury increased the early response gene Egr-1 and increased expression of pro- and anti-inflammatory cytokines within 1 h. The injury induced granulocyte/macrophage colony-stimulating factor mRNA and matured monocytes to alveolar macrophages by 24 h. The mRNA for the surfactant proteins A, B, and C increased in the lungs by 24 h. The airway epithelium demonstrated dynamic changes in heat shock protein 70 (HSP70) over time. Serum cortisol levels did not increase, and induction of systemic inflammation was minimal. We conclude that a brief period of high V(T) ventilation causes a proinflammatory cascade, a maturation of lung monocytic cells, and an induction of surfactant protein mRNA.
机械通气是早产儿发生支气管肺发育不良的一个危险因素。15 分钟大潮气量（V(T)）通气在 3 小时内诱导小气道和肺实质中的炎症细胞因子表达。我们的目的是描述暴露于特定 15 分钟牵张损伤的胎儿羊中细胞因子和成熟反应对肺损伤的时间进展。在母体麻醉和剖腹产后，129 天胎龄的羔羊（每组 7-8 只）将头和胸部暴露在外。每只胎儿都进行插管，轻轻清除气道液。在维持胎盘支持的同时，胎儿接受无呼气末正压（PEEP）的 15 分钟递增 V(T)至 15 ml/kg 的通气，使用加热、加湿的 100%氮气。然后将胎儿放回子宫 1、6 或 24 小时。对照羊接受 2 cmH(2)O 的 PEEP 通气 15 分钟。评估肺和全身器官的组织样本。牵张损伤在 1 小时内增加了早期反应基因 Egr-1，并增加了促炎和抗炎细胞因子的表达。损伤在 24 小时内诱导粒细胞/巨噬细胞集落刺激因子 mRNA，并使成熟的单核细胞成熟为肺泡巨噬细胞。肺中表面活性蛋白 A、B 和 C 的 mRNA 在 24 小时时增加。气道上皮细胞的热休克蛋白 70（HSP70）随时间表现出动态变化。血清皮质醇水平没有升高，全身炎症的诱导很小。我们的结论是，短暂的高 V(T)通气会引起促炎级联反应、肺单核细胞的成熟以及表面活性蛋白 mRNA 的诱导。
