Division of Neonatology, Cardinal Glennon Children's Hospital, Saint Louis University , St. Louis, Missouri.
School of Women's and Infants' Health, University of Western Australia , Perth, Western Australia , Australia.
Am J Physiol Lung Cell Mol Physiol. 2019 May 1;316(5):L888-L893. doi: 10.1152/ajplung.00477.2018. Epub 2019 Mar 6.
Mechanical ventilation with normal tidal volumes (V) causes lung and systemic inflammation in preterm sheep. Mechanical ventilation is associated with bronchopulmonary dysplasia (BPD) in preterm infants, and the addition of budesonide to surfactant decreases BPD in clinical trials. Budesonide with surfactant will decrease the lung injury from mechanical ventilation for 24 h in preterm sheep. Lambs at 126 ± 1 day gestational age were delivered and randomized to either: ) surfactant (200 mg/kg) or ) surfactant mixed with budesonide (0.25 mg/kg) before mechanical ventilation with V of 7-8 ml/kg for 2, 6, or 24 h ( = 6 or 7/group). Lung physiology and budesonide levels in the plasma and the lung were measured. Lung tissue, bronchoalveolar lavage fluid (BALF), liver, and brain tissues were evaluated for indicators of injury. High initial budesonide plasma levels of 170 ng/ml decreased to 3 ng/ml at 24 h. Lung tissue budesonide levels were less than 1% of initial dose by 24 h. Although physiological variables were generally similar, budesonide-exposed lambs required lower mean airway pressures, had higher hyperoxia responses, and had more stable blood pressures. Budesonide decreased proinflammatory mRNA in the lung, liver, and brain. Budesonide also decreased total protein and proinflammatory cytokines in BALF, and decreased inducible nitric oxide synthase activation at 24 h. In ventilated preterm lambs, most of the budesonide left the lung within 24 h. The addition of budesonide to surfactant improved physiology, decreased markers of lung injury, and decreased systemic responses in liver and brain.
常频机械通气（V）可引起早产儿肺和全身炎症。机械通气与早产儿支气管肺发育不良（BPD）有关，而表面活性物质联合布地奈德治疗可减少临床试验中的 BPD。表面活性物质联合布地奈德治疗可降低早产儿机械通气 24 小时的肺损伤。妊娠 126±1 天的羔羊分娩后随机分为：）表面活性物质（200 mg/kg）或）表面活性物质混合布地奈德（0.25 mg/kg），然后进行机械通气，V 为 7-8 ml/kg，持续 2、6 或 24 小时（每组 6 或 7 只）。测量肺生理和血浆及肺中的布地奈德水平。评估肺组织、支气管肺泡灌洗液（BALF）、肝和脑组织的损伤指标。初始布地奈德血浆水平为 170 ng/ml，24 小时后降至 3 ng/ml。24 小时时肺组织布地奈德水平低于初始剂量的 1%。尽管生理变量通常相似，但布地奈德暴露的羔羊需要较低的平均气道压力，具有更高的高氧反应，且血压更稳定。布地奈德降低了肺、肝和脑中的促炎 mRNA。布地奈德还降低了 BALF 中的总蛋白和促炎细胞因子，并降低了 24 小时时诱导型一氧化氮合酶的激活。在机械通气的早产儿中，大部分布地奈德在 24 小时内离开肺部。表面活性物质中添加布地奈德可改善生理状况，降低肺损伤标志物，并降低肝和脑中的全身反应。
