胎粪诱导肺损伤及rhSOD的抗炎抗氧化作用研究

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(rhSOD)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1 ml/kg复制胎粪肺损伤模型,然后随机分为:对照组和给予rhSOD 5 mg/kg、10 mg/kg、20 mg/kg组.24 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,rhSOD各治疗组肺组织MPO活性显著降低(P分别<0.05、0.01和0.05),SOD活性显著增加(P均<0.05),NO含量显著下降(P分别<0.05、0.01和0.01),各治疗组经F检验,差异无显著性(P均>0.05);8-异前列腺烷含量下降(P分别<0.05、0.01和0.01),rhSOD 20 mg/kg组比rhSOD 5 mg/kg组更低(P=0.01),rhSOD 10 mg/kg组比rhSOD 5 mg/kg组略有下降,但差异无显著性(P=0.05);rhSOD 20 mg/kg组肺损伤病理评分明显减低(P<0.05),rhSOD 5 mg/kg、10 mg/kg组肺损伤病理评分略有下降,但差异无显著性(P均>0.05).各组肺组织湿/干重比、BALF蛋白含量、PPI的变化不明显(P均>0.05).结论:早期气管内给予单剂5、10或20 mg/kg rhSOD均可增加肺内SOD活性,减少脂质过氧化物产生,从而减轻胎粪诱导的大鼠肺炎症和过氧化损伤.

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

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.