Kopincova J, Mikolka P, Kolomaznik M, Kosutova P, Calkovska A, Mokra D
Biomedical Center Martin and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
Physiol Res. 2017 Sep 22;66(Suppl 2):S227-S236. doi: 10.33549/physiolres.933678.
Meconium aspiration syndrome (MAS) in newborns is characterized mainly by respiratory failure due to surfactant dysfunction and inflammation. Previous meta-analyses did not prove any effect of exogenous surfactant treatment nor glucocorticoid administration on final outcome of children with MAS despite oxygenation improvement. As we supposed there is the need to intervene in both these fields simultaneously, we evaluated therapeutic effect of combination of exogenous surfactant and selective inhibitor of NF-kappaB (IKK-NBD peptide). Young New Zealand rabbits were instilled by meconium suspension and treated by surfactant alone or surfactant in combination with IKK-NBD, and oxygen-ventilated for 5 h. PaO(2)/FiO(2), oxygenation index, oxygen saturation and ventilation efficiency index were evaluated every hour; post mortem, total and differential leukocyte counts were investigated in bronchoalveolar lavage fluid (BALF) and inflammatory, oxidative and apoptotic markers were assessed in lung tissue homogenates. Exogenous surfactant combined with IKK-NBD improved oxygenation, reduced neutrophil count in BALF and levels of IL-1beta, IL-6, p38 MAPK and caspase 3 in comparison with surfactant-only therapy. It seems that inhibition of inflammation may be strong supporting factor in surfactant treatment of MAS.
新生儿胎粪吸入综合征（MAS）的主要特征是由于表面活性剂功能障碍和炎症导致的呼吸衰竭。以往的荟萃分析并未证明外源性表面活性剂治疗或糖皮质激素给药对MAS患儿的最终结局有任何影响，尽管氧合有所改善。由于我们认为有必要同时在这两个领域进行干预，因此我们评估了外源性表面活性剂与NF-κB选择性抑制剂（IKK-NBD肽）联合治疗的效果。给年轻的新西兰兔滴入胎粪混悬液，单独用表面活性剂或表面活性剂与IKK-NBD联合治疗，并进行5小时的氧通气。每小时评估动脉血氧分压/吸入氧分数值（PaO₂/FiO₂）、氧合指数、血氧饱和度和通气效率指数；死后，检测支气管肺泡灌洗液（BALF）中的白细胞总数和分类计数，并评估肺组织匀浆中的炎症、氧化和凋亡标志物。与仅用表面活性剂治疗相比，外源性表面活性剂与IKK-NBD联合使用可改善氧合，减少BALF中的中性粒细胞计数以及白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、p38丝裂原活化蛋白激酶（p38 MAPK）和半胱天冬酶-3（caspase 3）的水平。似乎抑制炎症可能是MAS表面活性剂治疗的有力支持因素。
