重组人超氧化物歧化酶加强一氧化氮吸入治疗幼鼠急性胎粪肺损伤的实验研究

Recombinant human superoxide dismutase enhances the effect of inhaled nitric oxide in infant rats meconium aspiration lung injury

目的 探讨联合应用重组人超氧化物歧化酶 (recombinanthumansuperoxidedismatase ,rhSOD)和一氧化氮吸入 (inhalednitricoxide,iNO)对胎粪诱导幼鼠急性肺损伤的保护作用及可能机制。方法 32只雄性SD幼年大鼠 ,通过气管置管注入 2 0 %胎粪 1ml/kg建立幼鼠胎粪性肺损伤模型 ,随机分为 :( 1)对照组 (Control,C) :暴露于空气中 ;( 2 )NO吸入组 (iNO) :暴露于 2 0× 10 - 6 NO中 ;( 3)rhSOD组 (SOD) ) :rhSOD 2 0mg/kg·ml气管内注入并暴露于空气中 ;( 4 )联合应用 2 0× 10 - 6 NO和 2 0mg/kgrhSOD组 (iNO/SOD) ,暴露 2 4h后观察支气管肺泡灌洗液 (bronchoalveolarlavagefluid ,BALF)细胞数、肺组织匀浆髓过氧化物酶 (myeloperoxidase ,MPO)活性、丙二醛 (malonyldialdehyde,MDA)、一氧化氮 (nitricoxide,NO)含量和肺损伤病理改变。结果 与对照组比较 ,iNO组、SOD组BALF细胞数、MPO活性、肺损伤病理评分下降(P <0 0 5或 0 0 1)、iNO/SOD组较iNO组BALF细胞数、MPO活性进一步降低 (均P <0 0 5 ) ;但肺损伤病理评分差异无显著牲 ;与对照组比较 ,iNO组肺组织MDA、NO含量略有下降 ,但差异无意义 (均P >0 0 5 ) ,SOD组、iNO/SOD组肺组织MDA、NO含量显著下降 (P <0 0 5或 0 0 1) 。

Objective To evaluate the protective effect and mechanism of recombinant humansuperoxide dismutase (rhSOD) combined with inhaled nitric oxide (iNO) in infant rats with meconium aspiration acute lung iujury(ALI) .Methods 32 healthy male infant Sprage-Dawley rats were used. The model of ALI was established by infusing lml/kg of 20% newborn meconium suspension through endotracheal tube,and then randomized to 4 groups (8 in each): (1) Control group (C), exposure to room air; (2) iNO group,exposure to 20×10 -6 nitric oxide; (3) SOD group, infusing 20mg/kg rhSOD dissolved in l ml/kg 0 9% saline through endotracheal tube, followed by exposure to room air; (4) iNO/ SOD group,treatment with both 20mg/kg rhSOD and 20×10 -6 iNO. The animals were killed after 24h of treatments. The measurements included bronchoalveolar lavage fluid (BALF) cell counts, pulmonary myeloperoxidase (MPO) activity,malonyldialdehyde (MDA) and nitric oxide (NO) levels. Lung injury score was also evaluated.Results Compared with the C group, the rats in the iNO group, SOD group and iNO/SOD group had decreased BALF cell counts, MPO activity and lung injury score ( P <0 05 or 0 01 ) .Moreover, compared with the iNO group, iNO/SOD group had further decreased,BALF cell counts and MPO activity (all P <0 05) .Compared with the C group, pulmonary MDA and NO levels were decreased significantly in both SOD group and iNO/SOD group ( P <0 05 or 0 01 ) but not in the iNO group (all P >0 05).The iNO/SOD group hadlower pulmonary MDA and NO level than iNO group ( all P <0 05 ) .Conclusion 20mg/kg rhSOD intra-traeheal administration could enhance the effect of iNO in infant rats with meconium aspiration lung injury.