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

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］

Abstract:

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］