Role of extracellular superoxide dismutase in bleomycin-induced pulmonary fibrosis
Role of extracellular superoxide dismutase in bleomycin-induced pulmonary fibrosis
复制标题
DOI：
10.1152/ajplung.00058.2001
复制
发表时间：
2002-04-01
影响因子：
4.9
通讯作者：
Crapo, JD
中科院分区：
文献类型：
--
作者：
Bowler, RP;Nicks, M;Crapo, JD
博莱霉素的使用导致细胞内氧化应激，可导致肺纤维化。肺泡间质抗氧化剂在该模型中的作用尚不清楚。细胞外超氧化物歧化酶（EC-SOD）是主要的内源性细胞外抗氧化酶，在肺中含量丰富。我们推测EC-SOD在减轻博莱霉素引起的肺损伤中起重要作用。在气管内给药博莱霉素两周后，我们发现野生型小鼠肺EC-SOD升高106 +/- 25%。免疫组化染色显示损伤肺组织中EC-SOD大量升高。使用肺中特异性表达EC-SOD的小鼠，我们发现博来霉素给药2周后，博来霉素诱导的肺损伤组织学评估减少了53 +/- 14%，肺胶原含量减少了17 +/- 6%。我们得出结论，EC-SOD在减少博来霉素给药后细胞外自由基对肺损伤的程度方面起重要作用。
Bleomycin administration results in well-described intracellular oxidative stress that can lead to pulmonary fibrosis. The role of alveolar interstitial antioxidants in this model is unknown. Extracellular superoxide dismutase (EC-SOD) is the primary endogenous extracellular antioxidant enzyme and is abundant in the lung. We hypothesized that EC-SOD plays an important role in attenuating bleomycin-induced lung injury. Two weeks after intratracheal bleomycin administration, we found that wild-type mice induced a 106 +/- 25% increase in lung EC-SOD. Immunohistochemical staining revealed that a large increase in EC-SOD occurred in injured lung. Using mice that overexpress EC-SOD specifically in the lung, we found a 53 +/- 14% reduction in bleomycin-induced lung injury assessed histologically and a 17 +/- 6% reduction in lung collagen content 2 wk after bleomycin administration. We conclude that EC-SOD plays an important role in reducing the magnitude of lung injury from extracellular free radicals after bleomycin administration.