Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Am J Respir Crit Care Med. 2010 May 15;181(10):1098-105. doi: 10.1164/rccm.200912-1818OC. Epub 2010 Feb 4.
Premature newborns frequently require manual ventilation for resuscitation during which lung injury occurs. Although surfactant protein (SP)-D regulates pulmonary inflammation, SP-D levels are low in the preterm lung. Commercial surfactants for treatment of respiratory distress syndrome do not contain SP-D.
To determine whether addition of recombinant human SP-D (rhSP-D) to commercial surfactant influences lung inflammation in ventilated premature newborn lambs.
Prematurely delivered lambs (130 d gestation age) were resuscitated with 100% O(2) and peak inspiratory pressure 40 cm H(2)O for 20 minutes and then treated with Survanta or Survanta containing rhSP-D. Ventilation was then changed to regulate tidal volume at 8 to 9 ml/kg. At 5 hours of age lambs were killed for sample collection.
Sequential blood gas and tidal volume were similar in lambs treated with or without rhSP-D, indicating that lung immaturity and ventilatory stress used to support premature lambs were comparable between the two groups. Ventilation caused pulmonary inflammation in lambs treated with surfactant alone. In contrast, surfactant containing rhSP-D decreased neutrophil numbers in bronchoalveolar lavage fluid and decreased neutrophil elastase activity in lung tissue. IL-8 mRNA and IL-8 protein were significantly decreased in the +rhSP-D group lamb lungs, to 20% of those in controls. The addition of rhSP-D also rendered Survanta more resistant to plasma protein inhibition of surfactant function.
Treatment with rhSP-D-containing surfactant inhibited lung inflammation and enhanced the resistance of surfactant to inhibition, supporting its potential usefulness for prevention of lung injury in the preterm newborn.
早产儿经常需要进行人工通气复苏，在此过程中会发生肺损伤。虽然表面活性蛋白-D（SP-D）可调节肺部炎症，但早产儿肺中 SP-D 水平较低。用于治疗呼吸窘迫综合征的商业表面活性剂不包含 SP-D。
确定添加重组人 SP-D（rhSP-D）是否会影响通气早产儿羊的肺炎症。
早产羊（130 天胎龄）用 100%O₂ 和 40 cm H₂O 的吸气峰压复苏 20 分钟，然后用 Sur-vanta 或含有 rhSP-D 的 Sur-vanta 进行治疗。然后将通气改为调节 8 至 9 ml/kg 的潮气量。在 5 小时时处死羔羊以采集样本。
rhSP-D 治疗或不治疗的羔羊的血气和潮气量呈连续变化，表明两组肺不成熟和支持早产儿的通气压力相似。单独用表面活性剂处理的羔羊通气引起肺部炎症。相比之下，含有 rhSP-D 的表面活性剂减少了支气管肺泡灌洗液中的中性粒细胞数量，并降低了肺组织中的中性粒细胞弹性蛋白酶活性。IL-8 mRNA 和 IL-8 蛋白在 +rhSP-D 组羔羊肺中显著降低，降至对照组的 20%。rhSP-D 的添加还使 Sur-vanta 更能抵抗血浆蛋白抑制表面活性剂的功能。
rhSP-D 包含的表面活性剂治疗抑制了肺炎症，并增强了表面活性剂对抑制的抵抗力，支持其在预防早产儿肺损伤方面的潜在用途。
