Kosutova Petra, Nemcova Nikolett, Kolomaznik Maros, Mokra Daniela, Calkovska Andrea, Mikolka Pavol
Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 01 Martin, Slovakia.
Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 01 Martin, Slovakia.
Antioxidants (Basel). 2022 Dec 25;12(1):37. doi: 10.3390/antiox12010037.
Aspirated meconium into a newborn's airways induces the transcription of pro-oxidative mediators that cooperate in the pathogenesis of inflammatory changes and may negatively affect the commonly used exogenous surfactant therapy. However, inflammation is not treated at present, nor is the time dependence of oxidative damage known. The aim of our study was to describe the time course of oxidative stress marker production during meconium aspiration syndrome (MAS) and its relationship to leukocyte infiltration. New Zealand rabbits were instilled with saline or meconium suspension and ventilated for 5.5 h. Respiratory parameters were recorded and blood samples were taken before meconium application and in time intervals of 15 and 30 min, 1.0, 1.5, 3.5 and 5.5 h after application to evaluate oxidative markers and differential leukocytes count. Meconium aspiration led to a worsening of respiratory parameters and a decrease in leukocytes in the first 15 min. Changes in leukocytes were correlated both with nitrotyrosine (3NT) levels and thiobarbituric acid reactive substance (TBARS) levels, with the latter also related to changes in neutrophil count. The production of 3NT and TBARS increased in 1.5 and 3.5 h, respectively, in different ways, suggesting more than one source of oxidative agents and a potential risk of exogenous surfactant inactivation in a short time. We observed that MAS triggered neutrophil migration to the alveolar space and activation, as shown by the increased expression of pro-inflammatory cytokines and generation of indicators of oxidative damage to proteins and lipids during the time period when iNOS and NO metabolites were released.
新生儿气道内吸入胎粪会诱导促氧化介质的转录，这些介质在炎症变化的发病机制中相互作用，可能会对常用的外源性表面活性剂治疗产生负面影响。然而，目前炎症并未得到治疗，氧化损伤的时间依赖性也尚不明确。我们研究的目的是描述胎粪吸入综合征（MAS）期间氧化应激标志物产生的时间进程及其与白细胞浸润的关系。给新西兰兔滴注生理盐水或胎粪悬液，并通气5.5小时。记录呼吸参数，并在滴注胎粪前以及滴注后15分钟、30分钟、1小时、1.5小时、3.5小时和5.5小时的时间间隔采集血样，以评估氧化标志物和白细胞分类计数。胎粪吸入导致呼吸参数恶化以及最初15分钟内白细胞减少。白细胞变化与硝基酪氨酸（3NT）水平和硫代巴比妥酸反应性物质（TBARS）水平均相关，后者也与中性粒细胞计数变化有关。3NT和TBARS的产生分别在1.5小时和3.5小时以不同方式增加，这表明氧化因子有多种来源以及外源性表面活性剂在短时间内失活的潜在风险。我们观察到，MAS触发了中性粒细胞向肺泡腔的迁移和活化，这表现为在诱导型一氧化氮合酶（iNOS）和一氧化氮代谢产物释放期间促炎细胞因子表达增加以及蛋白质和脂质氧化损伤指标的产生增加。
