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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
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MT 4 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。［中国当代儿科杂志，2009，11（7）：581-584］
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.［Chin J Contemp Pediatr, 2009, 11 (7):581-584］
自由基 / 抗氧化酶 / 肺损伤 / 褪黑素 / 高氧 / 大鼠 / 新生
Free radical / Antioxidant / Lung damage / Melatonin / Hyperoxia / Neonatal rats
［1］Asikainen TM, White CW. Pulmonary antioxidant defenses in the preterm newborn with respiratory distress and bronchopulmonary dysplasia in evolution: implications for antioxidant therapy［J］. Antioxid Redox Signal, 2004, 6(1):155-167.
［2］Reiter RJ. Oxidative damage in the central nervous system: protection by melatonin ［J］. Prog Neurobiol, 1998, 56(3):359-384.
［3］Gitto E, Reiter RJ, Sabatino G, Buonocore G, Romeo C, Gitto P, et al. Correlation among cytokines, bronchopulmonary dysplasia and modality of ventilation in preterm newborns: improvement with melatonin treatment ［J］. J Pineal Res, 2005, 39(3):287-293.
［4］富建华，薛辛东．慢性肺疾病早产鼠BALF及肺组织中脂质过氧化的同步研究［J］．中国优生与遗传杂志，2004，12(6)：32-37．
［5］Ogihara T, Hirano K, Morinobu T, Kim HS, Hiroi M, Ogihara H, et al. Raised concentration of aldehyde lipid peroxidation products in premature infants with chronic lung disease［J］. Arch Dis Child Fetal Neonatal Ed, 1999, 80(1):F21-F25.
［6］Kaarteenaho-Wiik R, Kinnula VL. Distribution of antioxidant enzymes in developing human lung, respiratory distress syndrome, and bronchopulmonary dysplasia［J］. J Histochem Cytochem, 2004, 52(9):1231-1240.
［7］Asikainen TM, Raivio KO, Saksela M, Kinnula VL. Expression and developmental profile of antioxidant enzymes in human lung and liver ［J］. Am J Respir Cell Mol Biol, 1998, 19(6):942-949.
［8］Dani C, Cecchi A, Bertini G. Role of oxidative stress as physiopathologic factor in the preterm infant［J］. Minerva Pediatr, 2004, 56(4):381-394.
［9］Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ. One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?［J］. J Pineal Res, 2007, 42(1):28-42.
［10］Bandyopadhyay D, Biswas K, Bandyopadhyay U, Reiter RJ, Banerjee RK. Melatonin protects against stress-induced gastric lesions by scavenging the hydroxyl radical［J］. J Pineal Res, 2000, 29(3):143-151.
［11］Rodriguez C, Mayo JC, Sainz RM, Antolín I, Herrera F, Martín V, et al. Regulation of antioxidant enzymes: a significant role for melatonin［J］. J Pineal Res, 2004, 36(1):1-9.
［12］Giacomo CG, Antonio M. Melatonin in cardiac ischemia/reperfusion-induced mitochondrial adaptive changes ［J］. Cardiovasc Hematol Disord Drug Targets, 2007, 7(3):163-169.
［13］Maharaj DS, Glass BD, Daya S. Melatonin: new places in therapy［J］. Biosci Rep, 2007, 27(6):299-320.
［14］侯伟，刘海燕，李丹，周戬平，陈玺.新生大鼠高氧肺损伤血管内皮生长因子蛋白及其mRNA表达变化研究［J］.中国当代儿科杂志，2008，10（2）：207-210.
［15］杜靖，杜立中，蒋静静，康兰芳，吴西玲.一氧化氮对新生鼠高氧肺损伤时表面活性蛋白A和肺甘露糖结合力的影响［J］.中国当代儿科杂志，2006，8（6）：486-490.
［16］Jahnke G, Marr M, Myers C, Wilson R, Travlos G, Price C. Maternal and developmental toxicity evaluation of melatonin administration orally to pregnant Sprague-Dawley rats［J］. Toxicol Res, 1999, 50(2):271-279.
