胎粪诱导肺损伤及rhSOD的抗炎抗氧化作用研究

Anti-inflammation and anti oxidation effects of recombinant human superoxide dismutase on acute lung injury induced by meconium aspiration in infant rats

目的 :观察早期气管内给予抗氧化剂重组人超氧化物歧化酶 (rh SOD)对胎粪诱导大鼠急性肺损伤的肺内脂质过氧化物和抗氧化物的产生及其炎症损伤的影响 ,探讨抗氧化干预的作用及机制。方法 :32只雄性 SD大鼠 ,由气管置管注入胎粪 1ml/kg复制胎粪肺损伤模型 ,然后随机分为 :对照组和给予 rh SOD5 mg/kg、10 mg/kg、2 0 mg/kg组。 2 4 h后取材 ,观察大鼠肺组织的湿 /干重比、支气管肺泡灌洗液 (BALF)蛋白含量及肺通透指数(BALF蛋白含量 /血浆蛋白含量 ,PPI) ;利用比色法检测肺匀浆髓过氧化物酶 (MPO)活性、一氧化氮 (NO)含量及超氧化物歧化酶 (SOD)活性 ;EIA法检测肺脂质过氧化物 8-异前列腺烷含量。结果 :与对照组比较 ,rh SOD各治疗组肺组织 MPO活性显著降低 (P分别 <0 .0 5、0 .0 1和 0 .0 5 ) ,SOD活性显著增加 (P均 <0 .0 5 ) ,NO含量显著下降(P分别 <0 .0 5、0 .0 1和 0 .0 1) ,各治疗组经 F检验 ,差异无显著性 (P均 >0 .0 5 ) ;8-异前列腺烷含量下降 (P分别 <0 .0 5、0 .0 1和 0 .0 1) ,rh SOD2 0 mg/kg组比 rh SOD5 mg/kg组更低 (P=0 .0 1) ,rh SOD10 mg/kg组比 rh SOD5mg/kg组略有下降 ,但差异无显著性 (P=0 .0 5 ) ;rh SOD2 0 mg/kg组肺损伤病理评分明显减低 (P<0 .0 5 ) ,rh SOD5 mg/kg、10

Objective: To investigate the anti inflammation and anti oxidation effects of recombinant human CuZn superoxide dismutase(rhSOD) on acute lung injury(ALI) induced by meconium aspiration in rats. Methods: 1 ml/kg of 20% human newborn meconium suspension was intratracheally (IT) administrated to induce the model of ALI in 32 male Sprage Dawley rats, and the animals were then randomized to 4 groups:3 treatment groups with IT administration of 5,10 and 20 mg/kg rhSOD dissolved in 1 ml/kg saline and the control group with IT administration of 1 ml/kg saline.The animals were killed after 24 h of treatments.The measurements included lung tissue wet/dry ratio,broncho alveolar lavage fluid (BALF) protein,BALF protein/plasma protein (pulmonary permeabi lity index,PPI),lung myeloperoxidase (MPO) and superoxide dismutase (SOD) activity,nitric oxide (NO) and 8 isoprostane levels.Lung injury score was also evaluated. Results: Compared with the control group,pulmonary MPO activity,NO and 8 isoprostane levels were significantly decreased and SOD activity was markedly increased in all rhSOD treatment groups( P <0.05 or 0.01).Compared with the rhSOD 5 mg/kg group,pulmonary 8 isoprostane level was further low in the rhSOD 20 mg/kg group( P =0 01).Lung injury score was decreased in rhSOD 20 mg/kg group ( P <0 05).But there were no statistically differences in lung wet/dry,BALF protein and PPI among all groups. Conclusion: The results suggest that a single IT dose of 5,10 or 20 mg/kg rhSOD can prevent lung damages in rats with ALI following meconium aspiration.