实验性胎粪吸入性肺炎一氧化氮吸入干预的研究

Effects of inhaled nitric oxide on rabbits with meconium aspiration pneumonia

目的 探讨在不同氧浓度下吸入CD11b不同浓度一氧化氮 (nitricoxide ,NO)对实验性胎粪吸入性肺炎肺损伤及肺中性粒细胞表面粘附分子CD11b表达的影响 ,为对该病是否适宜早期NO吸入干预提供实验室依据。方法 建立胎粪吸入性肺炎模型兔 ,对常频机械通气下的胎粪吸入性肺炎家兔在 2 1%或 10 0 %的氧浓度下分别给予 6× 10 -6、10× 10 -6、2 0× 10 -6的NO干预 12h ,通过图像分析处理测量肺泡间隔平均距离 ,病理切片检查评估肺损伤程度 ;测定肺组织髓过氧化物酶(myeloperoxidase ,MPO)活性 ,并采用流式细胞术检测肺泡灌洗液中性粒细胞表面粘附分子CD11b的表达。结果 在相同氧浓度下 ,NO吸入能显著改善氧合。病理结果表明 ,各干预组和非干预组均可见严重的中性粒细胞浸润到肺间质 ,轻到中度的肺出血、肺水肿、肺透明膜形成以及中性粒细胞移行到肺泡腔 ,各吸入NO干预组上述病理变化均有减轻趋势。相同氧浓度下 10× 10 -6、2 0× 10 -6的NO吸入干预组肺MPO活性分别显著低于非干预组 (P均 <0 .0 5 ) ;10 0 %氧浓度下 2 0× 10 -6NO干预组MPO活性显著低于 2 1%氧浓度下同一NO干预组 [(1.4± 0 .3)U/gvs (2 .0± 0 .1)U/g,P <0 .0 5 ]。在 2 1%或 10 0 %氧浓度下 ,10× 10 -6、2 0× 10

Objective To evaluate effects of inhaled nitric oxide (iNO) on the expression of lung neutrophil adhesion molecule CD_ 11b in experimental meconium aspiration pneumonia treated with conventional mechanical ventilation under room air or 100% O_2. Methods Rabbits were randomly allocated to 10 groups ( n =60), 6 of each group. Control or meconium aspiration pneumonia model groups were inhaled with room air or 100% O_2. Six treatment groups were treated with continuous NO inhalation at the doses of 6×10 -6 , 10×10 -6 and 20×10 -6 , respectively for 12 hours under room air or 100% O_2. The ratio of wet/dry (W/D) lung weight, alveolar septal width (ASW), myeloperoxidase (MPO) activity and lung injury score were measured. The expression of CD_ 11b in neutrophils of the bronchoalveolar lavage fluid (BALF) was detected with flow cytometry. Results After 12 hours ventilation, the oxygenation was maintained better in treatment groups under different O_2 concentrations than that in model groups. Inflammatory evidence was found in lungs from all the model groups and treatment groups, which was characterized by serious inflammatory cell infiltration in alveolar space and hyaline membrane formation. The lung inflammation was decreased in all groups with nitric oxide inhalation. The ratio of W/D lung weight and ASW among different groups had no significant difference. MPO activities were significantly decreased in groups treated with 10×10 -6 and 20×10 -6 iNO compared with the model groups [with the concentration of 21% O_2, (1.8±0.2) U/g vs (4.4±0.5) U/g and (2.0±0.1) U/g vs (4.4±0.5) U/g;with the concentration of 100% O_2, (1.7±0.4) U/g vs (2.8±0.5) U/g and (1.4±0.3) U/g vs (2.8±0.5) U/g, P <0.05, respectively]. MPO activities in the 20×10 -6 iNO group under 100%O_2 were significantly reduced compared with those under 21%O_2 [(1.4±0.3 )U/g vs (2.0±0.1) U/g, P <0.05]. Nitric oxide inhalation with the doses of 10×10 -6 and 20×10 -6 significantly decreased the expression of CD_ 11b (MFI) in neutrophils of the BALF compared with the expressions in model groups without NO treatment (with 21%O_2, 121±20 vs 392±204 and 112±30 vs 392±204;with 100% O_2, 113±24 vs 293±65 and 102±14 vs 293±65, P <0.05, respectively). Under the same iNO dose (10×10 -6 or 20×10 -6 ) no statistic difference was found between groups of different inspired oxygen concentrations (21% and 100%). Conclusions Inhaled nitric oxide with the doses of 10×10 -6 to 20×10 -6 could significantly down-regulate the CD_ 11b expression in neutrophil of the BALF and reduce the neutrophil sequestration and MPO activity in rabbit lungs, which may decrease the lung inflammation process in meconium aspiration pneumonia.