EXTRACELLULAR SUPEROXIDE DISMUTASE IN PULMONARY FIBROSIS

肺纤维化中的细胞外超氧化物歧化酶

• 批准号: 6208816
• 负责人: CHERYL L FATTMAN
• 金额: $ 3.24万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-03 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6208816
• 关键词: extracellular; genetically modified animals; laboratory mouse; nitric oxide; oxidative stress; pulmonary fibrosis /granuloma; superoxide dismutase; superoxides

Interstitial pulmonary fibrosis is a potentially lethal, chronic response to lung injury. Although the biochemical mechanisms involved in the pathogenesis of interstitial pulmonary fibrosis are poorly understood, reactive oxygen species, which are known to play a role in inflammatory reactions, are believed to be involved in the progression of this disease. It has been proposed that the antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), can protect against the progression of pulmonary fibrosis. To test the hypothesis that EC-SOD plays a central role in this disease, transgenic mice that overexpress EC-SOD and knockout mice that do not express EC-SOD will be utilized in a model of bleomycin- induced pulmonary fibrosis. We will determine whether altered levels of EC-SOD in transgenic and knockout mice alters the response to bleomycin-induced lung injury. In addition, we will examine EC-SOD expression and1or biodistribution during the early stages of fibrotic injury, to determine if alterations in EC-SOD activity early in the development of the disease are critical to the pathogenesis of pulmonary fibrosis. Finally, we will examine the interactive effects of nitric oxide, superoxide and EC-SOD in our model to determine if nitric oxide is involved in the oxidative damage associated with pulmonary fibrosis.

间质性肺纤维化是肺损伤的一种潜在致命的慢性反应。尽管间质性肺纤维化发病机制中涉及的生化机制知之甚少，但已知在炎症反应中起作用的活性氧被认为参与了该疾病的进展。已经提出，抗氧化酶，细胞外超氧化物歧化酶（EC-SOD），可以防止肺纤维化的进展。为了检验EC-SOD在该疾病中起核心作用的假设，将在博来霉素诱导的肺纤维化模型中使用过表达EC-SOD的转基因小鼠和不表达EC-SOD的敲除小鼠。我们将确定转基因小鼠和基因敲除小鼠EC-SOD水平的改变是否会改变对博莱霉素诱导的肺损伤的反应。此外，我们还将检测纤维化损伤早期EC-SOD的表达和/或生物分布，以确定疾病发展早期EC-SOD活性的改变是否对肺纤维化的发病机制至关重要。最后，我们将研究一氧化氮，超氧化物和EC-SOD在我们的模型中的相互作用，以确定一氧化氮是否参与肺纤维化相关的氧化损伤。