TOXICOLOGY OF PULMONARY OXIDANT INJURY IN AGING

增龄过程中肺力学的进行性恶化 已经被反复记录在案。衰老的生物化学方面 肺受到的关注要少得多，尤其是， 肺生物能量学还没有被研究过。 衰老肺中的生物能量学对 细胞的活性和寿命，因此，维持 适当的器官功能和对疾病和伤害的抵抗力。这 该项目将检验一种假设，即老年人的肺有一种 生物能量新陈代谢能力与 成人器官。具体地说，肺上皮将是 调查的重点。这个肺表面是气体的位置 因此，Exchange是许多类型的 肺部损伤。该假说预测上皮细胞 老年人的肺部对损伤的反应效率会较低。至 对此进行研究，一种可复制的氧化性肺损伤模型 是通过急性暴露(8小时)到3小时而形成的 臭氧浓度。在这种模式中，具体和独立 上皮损伤、细胞增殖和修复的阶段 已经被定义了。这些阶段中的每一个都可以在 伤害等级定义为轻、中、重，按 上皮损伤的程度。要全面评估 这种典型的氧化剂损伤的生物能量后果， 线粒体和细胞质的生物能量代谢将 调查过了。此外，这种损伤的细胞后果，既有 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 将与出现的形态变化相关联 在整个器官和分离的II型肺上皮细胞中。 这些综合研究将提供有关 衰老对正常健康人肺生物能量学的影响 哺乳动物和期间的一种化学品造成肺损伤的情况 这是许多常见肺毒素的典型特征。

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.