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TOXICOLOGY OF PULMONARY OXIDANT INJURY IN AGING

TOXICOLOGY OF PULMONARY OXIDANT INJURY IN AGING
衰老过程中肺氧化损伤的毒理学
批准号:
3119128
负责人:
MARK R MONTGOMERY
金额:
$7.26万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-08-01 至 1993-07-31

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项目成果

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中文摘要
翻译
衰老过程中肺力学逐渐恶化 已被多次记载。 衰老的生化方面 肺部受到的关注要少得多,特别是 肺生物能学根本没有被研究过。 衰老肺部的生物能学对于 细胞活力和寿命,从而维持 适当的器官功能以及对疾病和损伤的抵抗力。 这个 该项目将检验以下假设:衰老的肺具有 与正常人相比,生物能量代谢能力下降 成人器官。 具体来说,肺上皮是 调查重点。 肺表面是气体的场所 交换,因此,是许多类型的初始站点 肺部损伤。 该假说预测上皮细胞 老化的肺部对损伤的反应效率较低。 至 研究这一点,建立了一个可重复的氧化性肺损伤模型 使用急性暴露(8小时)至三 臭氧浓度。 在这个模型中,特定的和单独的 上皮损伤、细胞增殖和恢复阶段 已被定义。 这些阶段中的每一个都可以在 伤害等级定义为轻度、中度和重度 上皮损伤的程度。 为全面评估 这种典型的氧化损伤的生物能后果, 线粒体和细胞质生物能代谢 调查了。 此外,这种损伤的细胞后果, 在成年和老年动物中,将以脂质和 蛋白质损伤和防御反应。 所有生化研究 将与出现的形态变化相关 在整个器官和孤立的 II 型肺上皮中。 这些综合研究将提供有关 衰老对正常健康人肺生物能的影响 哺乳动物以及在化学物质造成肺损伤的情况下 这是许多常见肺部毒素的典型特征。
英文摘要
Progressive deterioration of pulmonary mechanics during aging has been documented repeatedly. Biochemical aspects of aging in the lung have received much less attention, and in particular, pulmonary bioenergetics have not been investigated at all. Bioenergetics in the aging lung are of immense importance to cellular viability and longevity, and hence, to maintenance of proper organ function and resistance to disease and injury. This project will examine the hypothesis that the aged lung has a decreased capacity for bioenergetic metabolism compared to the adult organ. Specifically, the pulmonary epithelium will be the focus of investigation. This lung surface is the site of gas exchange and as such, is the initial site for many types of pulmonary injury. The hypothesis predicts that the epithelial cells in aged lungs will respond less efficiently to injury. To investigate this, a reproducible model of oxidant lung injury has been developed using acute exposure (8 hours) to three concentrations of ozone. In this model, specific and separate phases of epithelial injury, cellular proliferation and recovery have been defined. Each of these phases may be ovserved during graded levels of injury defined as mild, moderate and severe by the extent of epithelial damage. To fully evaluate the bioenergetic consequences of this typical oxidant injury, both mitochondrial and cytoplasmic bioenergetic metabolism will be investigated. Also, the cellular consequences of this injury, both in adult and aged animals, will be quantitated in terms of lipid and protein damage and defensive responses. All biochemical studies will be correlated with the morphoetric alterations appearing both in the whole organ and in isolated Type II pulmonary epithelium. These combined studies will provide the first information on the effects of aging on pulmonary bioenergetics in the noral, healthy mammal and during the situation of lung injury from a chemical that is typical of numerous common pulmonary toxins.
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TOXICOLOGY OF PULMONARY OXIDANT INJURY IN AGING
  • 批准号:
    3119131
  • 项目类别:
  • 资助金额:
    $7.41万
  • 财政年份:
    1988
  • 负责人:
    MARK R MONTGOMERY
  • 依托单位:
TOXICOLOGY OF PULMONARY OXIDANT INJURY IN AGING
  • 批准号:
    3119132
  • 项目类别:
  • 资助金额:
    $7.33万
  • 财政年份:
    1988
  • 负责人:
    MARK R MONTGOMERY
  • 依托单位:
TOXICOLOGY OF PULMONARY OXIDANT INJURY IN AGING
  • 批准号:
    3119130
  • 项目类别:
  • 资助金额:
    $7.36万
  • 财政年份:
    1988
  • 负责人:
    MARK R MONTGOMERY
  • 依托单位:
TOXICOLOGY OF PULMONARY OXIDANT INJURY IN AGING
  • 批准号:
    3119133
  • 项目类别:
  • 资助金额:
    $7.52万
  • 财政年份:
    1988
  • 负责人:
    MARK R MONTGOMERY
  • 依托单位:
海外基金