SALT AND WATER TRANSPORT IN THE ALCOHOLIC LUNG

酒精肺中盐和水的运输

• 批准号: 6724375
• 负责人: Douglas C. Eaton
• 金额: $ 21.34万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6724375
• 关键词: alcoholism /alcohol abuse; alveolar macrophages; biological fluid transport; biological signal transduction; edema; electrolyte balance; electrophysiology; glucocorticoids; laboratory rat; lung injury; polymerase chain reaction; respiratory epithelium; salts; sodium channel; sodium chloride; sodium ion; tight junctions; tissue /cell culture; transforming growth factors; voltage /patch clamp; water; western blottings

DESCRIPTION (provided by applicant): Salt and water transport by lung epithelial cells is critical for normal clearance of fluid in the developing and mature lungs. A delicate balance between alveolar fluid secretion and absorption results in a thin fluid layer on the surface of the airways that helps promote pulmonary gas exchange and mucociliary clearance of foreign particles from the lung. The alveolar epithelial barrier formed by lung epithelial cells and tight junctions between the cells play a key role in this process, and disruption of the barrier function can result in alveolar flooding. Chronic alcohol exposure appears to compromise the alveolar barrier. Nonetheless, compensatory increases in salt transport in the alcoholic lung appear to be sufficient to maintain approximately normal levels of airway surface fluid. However, alcoholic lungs when challenged by any significant stress (like major trauma or sepsis) are much more likely to develop edema implying that the salt and water transport mechanisms cannot respond to increased demand as nonalcoholic lungs can. It is hypothesized that alcohol-induced changes in epithelial barrier function and transport mechanisms predispose the lungs to acute edematous lung injury. While there is now substantial evidence that the maintenance of salt and water transport is a strongly regulated, energy-dependent process, the pathways for salt and water transport are not clearly defined in the normal lung, let alone how they are modified in the alcoholic lung. It does seem likely that some regulatory mechanism controlling the response of lung salt and water transport stress is abnormal in alcoholic lungs. It is hypothesized that abnormal glucocorticoid and TGF-beta responsiveness of lung epithelial cells prevents stress-induced increases in lung salt and water transport in alcoholic lungs.There are three specific aims of this proposal. The first aim is to determine if transport characteristics of the alcoholic lung are different from normal lung. The second aim is to determine how transport in stressed alcoholic lung differs from normal and alcoholic lung. The third aim to elucidate the cellular mechanisms responsible for alcohol-induced changes in lung transport. These experiments will improve our understanding of how chronic alcohol exposure alters alveolar fluid balance under normal and stressful conditions, and help in devising therapeutic strategies to prevent edematous lung injury.

描述（由申请人提供）： 肺上皮细胞的盐和水转运对于发育和成熟肺中液体的正常清除至关重要。肺泡液体分泌和吸收之间的微妙平衡导致气道表面上的薄液体层，其有助于促进肺气体交换和粘膜纤毛从肺中清除外来颗粒。由肺上皮细胞和细胞之间的紧密连接形成的肺泡上皮屏障在此过程中起关键作用，屏障功能的破坏可导致肺泡灌洗液。慢性酒精暴露似乎会损害肺泡屏障。尽管如此，酒精性肺中盐转运的代偿性增加似乎足以维持气道表面液体的大致正常水平。然而，当受到任何重大压力（如重大创伤或败血症）的挑战时，酒精性肺更有可能发生水肿，这意味着盐和水的运输机制不能像非酒精性肺那样对增加的需求做出反应。据推测，酒精诱导的上皮屏障功能和转运机制的变化易使肺发生急性水肿性肺损伤。虽然现在有大量证据表明盐和水的维持 虽然盐和水的转运是一个受强烈调控的能量依赖性过程，但盐和水的转运途径在正常肺中并不清楚，更不用说它们在酒精性肺中是如何被改变的了。酒精性肺中控制肺盐和水运输应激反应的某些调节机制似乎确实异常。据推测，异常的糖皮质激素和TGF-β反应的肺上皮细胞防止应力诱导的增加，在酒精lungs.There是三个具体的目的，这个建议的肺盐和水运输。第一个目的是确定酒精性肺的转运特性是否与正常肺不同。第二个目的是确定应激酒精性肺的转运与正常和酒精性肺的不同。第三个目的是阐明细胞机制负责酒精诱导的肺转运的变化。 这些 实验将提高我们对慢性酒精暴露如何改变肺泡液的理解 在正常和压力条件下的平衡，并帮助设计治疗策略，以防止水肿性肺损伤。