Mesothelial Lubrication and Pleural Homeostatsis

间皮润滑和胸膜稳态

• 批准号: 6917022
• 负责人: STEPHEN H LORING
• 金额: $ 32.81万
• 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/6917022
• 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、心包腔和腹膜腔包含的器官必须能够改变形状和大小，并在腔内滑动以正常发挥功能。为了促进肺、心脏和腹部内脏改变形状和大小以及相对于体壁移动的能力，这些腔及其内容物被良好地润滑，允许器官在其容器中和自身上几乎无摩擦地滑动。我们建议研究的流体动力学机制的润滑mesothelium表面的重要性。我们的假设是，湿mesothelium表面对彼此的滑动导致液体中的流体动力学压力，从而降低最大剪切应力，并通过防止脆弱的mesothelium细胞之间的接触，更均匀地分配液体，并调节液体体积来防止细胞损伤。在我们的研究表明是否mesothelial表面接触的程度上，我们的结果将显示胸膜腔几何形状和力学的两种矛盾观点中的任何一种在体内应用的程度。 在目标1中，我们将使用落射荧光显微镜来探索润湿的mesothelium表面的滑动导致可逆平滑（变形）并增加表面之间的液体层厚度的均匀性的证据。在目标2中，我们将使用旋转和线性滑动摩擦计来测量滑动润湿介层表面的剪切力（即。例如，摩擦学行为）以确定剪切力对速度、法向应力、历史和润滑流体性质的依赖性。在目标3中，我们将探索与呼吸期间肺滑动相关的流体动力学机制，其可以循环胸膜液体，重新分配胸膜间隙中的液体，并通过控制胸膜液体经由淋巴通道的流出来调节液体体积。在目标4中，我们将使用扫描电子显微镜观察剪切应力引起的间皮细胞组织学变化。研究的各个方面都将得到三维计算流体动力学和有限元模型的支持。间皮细胞的破坏可导致纤维化和粘连。就间皮润滑保持间皮完整性而言，它对健康至关重要。我们的目标是了解这些正常的生理现象。