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: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3119128
• 关键词: NAD(H) phosphate; aging; animal old age; bioenergetics; catalase; cell growth regulation; environmental toxicology; enzyme linked immunosorbent assay; enzyme mechanism; histology; laboratory rat; lung disorder; mature animal; membrane permeability; mitochondria; nicotinamide adenine dinucleotide; nucleoside monophosphate; oxidative phosphorylation; ozone; physical chemical interaction; respiratory epithelium; respiratory gas transport; respiratory toxin; statistics /biometry; superoxide dismutase; tocopherols

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.

肺力学在衰老过程中的进行性恶化 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