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TOXICOLOGY OF PULMONARY OXIDANT INJURY IN AGING

衰老过程中肺氧化损伤的毒理学

基本信息

批准号：
3119133
负责人：
MARK R MONTGOMERY
金额：
$ 7.52万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-08-01 至 1994-07-31
项目状态：
已结题

项目摘要

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.

衰老过程中肺力学的进行性恶化被反复记录下来。衰老的生物化学方面肺受到的关注要少得多，特别是，肺生物能量学根本没有被研究过。老化肺中的生物能量学对于细胞活力和寿命，因此，维持适当的器官功能和抵抗疾病和伤害。这该项目将检验老年肺具有生物能代谢能力降低，成人器官具体来说，肺上皮将是调查的重点。这个肺表面是气体交易所，因此，是许多类型的肺损伤该假说预测上皮细胞老年人的肺对损伤的反应会降低。到为了研究这一点，一种可重复氧化性肺损伤模型使用急性暴露（8小时）对三种臭氧浓度。在这个模型中，特定的和独立的上皮损伤、细胞增殖和恢复的阶段已被定义。这些阶段中的每一个都可以在损伤分级水平定义为轻度、中度和重度，上皮损伤的程度。为了全面评估这种典型的氧化损伤的生物能量后果，线粒体和细胞质的生物能代谢将是研究了此外，这种损伤的细胞后果，在成年和老年动物中，将根据脂质和蛋白质损伤和防御反应。所有生化研究将与形态计量学上的改变相关，在整个器官和分离的II型肺上皮中。这些综合研究将提供关于衰老对正常、健康人肺生物能量学的影响哺乳动物和在肺损伤的情况下，从化学品这是许多常见肺部毒素的典型特征