Mesothelial Lubrication and Pleural Homeostatsis

间皮润滑和胸膜稳态

• 批准号: 7074570
• 负责人: STEPHEN H LORING
• 金额: $ 31.7万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7074570
• 关键词: biomechanics; confocal scanning microscopy; epithelium; fluid flow; histology; laboratory mouse; laboratory rabbit; laboratory rat; lung; lymphatic circulation; mathematical model; microcapsule; morphometry; nonblood rheology; pericardium; peritoneal cavity; pleural cavity; pulmonary respiration; scanning electron microscopy; shear stress; sheep; surface property; swine; video microscopy

DESCRIPTION (provided by applicant): The pleural, pericardial, and peritoneal cavities contain organs that must be able to change shape and size and to slide within their cavities to function normally. To facilitate the ability of the lungs, heart, and abdominal viscera to change shape and size and to move relative to the body wall, these cavities and their contents are well lubricated, allowing almost frictionless sliding of the organs in their container and on themselves. We propose to study the hydrodynamic mechanisms important for lubrication of mesothelial surfaces. Our hypothesis is that the sliding of wetted mesothelial surfaces against each other causes hydrodynamic pressures in the liquid that reduce maximal shear stresses and protect against cellular damage by preventing contact between delicate mesothelial cells, distributing the liquid more evenly, and regulating liquid volume. To the extent that our studies show whether or not mesothelial surfaces come into contact, our results will show to what extent either of the two contradictory views of pleural space geometry and mechanics applies in vivo. In Aim 1, we will use epi-fluorescence microscopy to explore evidence that sliding of wetted mesothelial surfaces causes reversible smoothing (deformation) and increases the uniformity of thickness of the liquid layer between the surfaces. In Aim 2, we will use rotational and linear sliding tribometers to measure shear force of sliding wetted mesothelial surfaces (i. e., tribological behavior) to determine the dependence of shear force on velocity, normal stress, history, and the nature of the lubricating fluid. In Aim 3, we will explore fluid dynamic mechanisms associated with the sliding of lungs during breathing that could circulate pleural liquid, redistribute liquid in the pleural space, and regulate liquid volume by controlling the efflux of pleural liquid via lymphatic channels. In Aim 4, we will visualize changes in mesothelial cell histology caused by shear stress using scanning electron microscopy. All aspects of the research will be supported by three-dimensional computational fluid dynamics and finite element models. Destruction of the mesothelium can lead to fibrosis and adhesions. To the extent that mesothelial lubrication preserves mesothelial integrity, it is vital to health. Our goal is to understand these normal physiological phenomena.

描述（由申请人提供）：胸膜腔、心包腔和腹膜腔中包含的器官必须能够改变形状和大小，并在腔内滑动才能正常工作。为了促进肺、心脏和腹部脏器改变形状和大小的能力，以及相对于体壁的移动，这些腔体及其内容物得到了良好的润滑，使它们在容器内和自身上的器官几乎无摩擦地滑动。我们建议研究间皮表面润滑的流体动力学机制。我们的假设是，湿润的间皮表面相互滑动会导致液体中的流体动力压力，从而减少最大剪切应力，并通过防止脆弱的间皮细胞之间的接触、更均匀地分布液体和调节液体体积来保护细胞免受损伤。在某种程度上，我们的研究表明间皮表面是否接触，我们的结果将表明胸膜空间几何和力学的两种相互矛盾的观点中的任何一种在多大程度上适用于体内。