褪黑素对高氧致新生鼠慢性肺疾病肺组织氧化/抗氧化系统的影响  

Effect of melatonin on hyperoxia-induced oxidant/antioxidant imbalance in the lung of neonatal rats with chronic lung disease

作　　者：潘丽[1] 许巍[1] 富建华[1] 薛辛东[1] 

机构地区：[1]中国医科大学附属盛京医院儿科,辽宁沈阳110004

出　　处：《中国当代儿科杂志》2009年第7期581-584,共4页Chinese Journal of Contemporary Pediatrics

基　　金：国家自然科学基金(编号30440056)

摘　　要：目的探讨近年来发现的高效抗氧化剂褪黑素(MT)对高氧致新生鼠慢性肺疾病(CLD)肺组织氧化/抗氧化系统的影响。方法采用高氧暴露(FiO2=0.85)致新生鼠CLD模型,足月新生鼠共90只随机分为3组(每组30只):空气对照组、高氧对照组、MT治疗组。空气对照组置于空气中,高氧对照组、MT治疗组(连同母鼠)置于玻璃氧箱中,维持FiO2为0.85;MT治疗组于生后0 d高氧暴露前30 min和生后每天给予MT4 mg/kg腹腔注射直至实验结束。每组分别于实验后3,7,14 d随机选取10只处死,观察肺组织形态改变,分别测定肺组织中总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)、谷胱苷肽过氧化物酶(GSH-Px)活性、髓过氧化物酶(MPO)、过氧化氢酶(CAT)、NO水平(以NO2-/NO3-衡量)以及丙二醛(MDA)含量改变。结果MT治疗组病理改变明显减轻。空气对照组、高氧对照组、MT治疗组T-AOC,SOD,GSH-Px及CAT活性随实验时间的延长均逐渐升高,但空气对照组、高氧对照组两组比较各项指标差异均无显著性(P>0.05),MT治疗组各项指标在实验各时点与空气对照组、高氧对照组相比均明显升高(P<0.05)。高氧对照组NO2-/NO3-,MDA水平以及MPO含量在3,7,14 d均高于空气对照组(P<0.05或0.01)。MT治疗组NO2-/NO3-,MDA水平以及MPO含量则明显降低,与高氧对照组比较差异具有显著性(P<0.05)。结论MT通过提高肺组织的抗氧化能力、抑制氧化应激反应,从而逆转了高氧致新生鼠CLD肺组织氧化/抗氧化系统失衡。Objective To study the effect of melatonin, a potent antioxidant both in vitro and in vivo, on hyperoxia-induced oxidant/antioxidant imbalance in the lung of neonatal rats with chronic lung disease （ CLD ）. Methods Ninety neonatal rats were randomly divided into three groups （n = 30 each） ： air-exposed, hyperoxia-exposed, melatonin-treated （4 mg/kg melatonin was administered 30 minutes before hyperoxia exposure and once daily after exposure）. CLD was induced by hyperoxia exposure （FiO2 =0.85）. Lung specimens were obtained 3, 7, and 14 days after exposure （n = 10 each） for histopathologic examination. The levels of total antioxidase capacity （T-AOC）, superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px）, myeloperoxidase （MPO）, catalase （CAT）, nitrite/nitrate, and malondialdehyde （MDA） in the lung were assayed by the spectrophotometer. Results The histopathologic examination showed that lung damage was obviously alleviated in the melatonin-treated group. The levels of T-AOC, GSH-Px, SOD and CAT in the lung were significantly higher in the melatonin-treated group than those in the other two groups at all time points （ P 〈 0.05 ）. The levels of MPO, nitrite/nitrate and MDA in the lung increased significantly in the untreated hypoxia-exposed group compared with those in the air-exposed group at all time points （P 〈 0.05 or 0.01 ） , while the levels of MPO, nitrite/ nitrate and MDA in the melatonin-treated group were significantly reduced as compared with the untreated hypoxia-exposed group （ P 〈 0.05 ）. Conclusions Melatonin may reverse oxidant/antioxidant imbalance in hyperoxia-induced lung disease, thus providing a protective effect against CLD in neonatal rats.

关 键 词：自由基 抗氧化酶 肺损伤 褪黑素 高氧 大鼠 新生 

分 类 号：R96[医药卫生—药理学]