DEVELOPMENT AND CONTROL OF PULMONARY ALVEOLAR STABILITY

这项申请建议继续进行多学科研究 肺泡稳定性的发展、控制和紊乱。 肺泡稳定性紊乱是呼吸系统的主要问题 新生儿的窘迫综合征，并对新生儿的 包括成人在内的其他常见肺部疾病的病理生理学 呼吸窘迫综合征和肺炎。该提案集中在两个方面 肺泡稳定性的相关决定因素。第一个是功能， 肺泡II型分泌物表面活性物质的结构与代谢 上皮细胞。二是肺泡上皮细胞的调节 表型。目标是：- L.研究II型细胞胆固醇代谢的调节 血浆脂蛋白在肺组织中的转运 强调内吞性脂蛋白受体的作用， 2.研究胞吞和胞吐的协同调节。 并检测血浆脂蛋白受体的作用 以及在这些事件中的特定信号通路， 3.确定特定结构要素在 表面活性脂蛋白代谢中的表面活性载脂蛋白， 4.研究分子机制、生理表现和 肺功能表面现象的理论模型， 5.为了确定物理刺激，特别是膨胀的影响， 关于肺泡区的生长和成熟。 6.鉴定肺泡上皮细胞的表型标志物 利用这些标记物研究上皮细胞的发育和调控 细胞表型。 这些研究的总体目的是加深我们对 肺泡稳定的基本过程和有助于新概念的提出 以及与肺泡紊乱相关的肺部疾病的治疗 稳定性或上皮成熟。

This application proposes to continue multidisciplinary studies of development, control and disorders of pulmonary alveolar stability. Disordered alveolar stability is the primary problem in respiratory distress syndrome of the newborn and contributes significantly to the pathophysiology of other common forms of lung disease including adult respiratory distress syndrome and pneumonia. The proposal focuses on two related determinants of alveolar stability. The first is the function, structure, and metabolism of surfactant: a secretion of type II alveolar epithelial cells. The second is the regulation of alveolar epithelial cell phenotype. The goals are :- l. to study the regulation of cholesterol metabolism in type II cells and the trafficking of plasma lipoproteins in the lung with a particular emphasis on the role of endocytotic lipoprotein receptors, 2. to investigate the co-ordinate regulation of endocytosis and exocytosis in type II cells and to examine the role of plasma lipoprotein receptors and specific signalling pathways in these events, 3. to determine the importance of specific structural elements in the surfactant apoproteins in the metabolism of surfactant lipoproteins, 4. to examine molecular mechanisms, physiological manifestations and theoretical models of surface phenomena in lung function, 5. to determine the effects of physical stimuli, particularly distension, on the growth and maturation of the alveolar region of the lung. 6. to characterize phenotypic markers of alveolar epithelial cells and using these markers study the development and regulation of epithelial cell phenotype. The overall purpose of these studies is to deepen our understanding of the processes underlying alveolar stability and to contribute to new concepts and treatments for lung diseases associated with disorders of alveolar stability or epithelial maturation.