STRUCTURAL DETERMINANTS OF GLOMERULAR PERMEABILITY

肾小球通透性的结构决定因素

• 批准号: 3246614
• 负责人: BARBARA S DANIELS
• 金额: $ 11.18万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1997-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3246614
• 关键词: actins; angiotensin II; calcium flux; capillary; confocal scanning microscopy; cytoskeleton; glomerular filtration; glomerulonephritis; laboratory rat; macromolecule; membrane model; membrane permeability; renal glomerulus; single cell analysis

The glomerulus is a complex filter with remarkably high hydraulic conductivity and low macromolecular permeability. Abnormalities of hydraulic conductivity and macromolecular permeability accompany most types of progressive renal disease, yet the understanding of the physiology and regulation of the glomerular permeability barrier is not well developed, probably due in part to the lack of models where glomerular function can be assessed independently of the hemodynamic and hormonal factors which contribute importantly, but not solely, to the permeance of water and macromolecules across the glomerular capillary wall. The development of two in vitro models of glomerular permeability whereby the contribution of discrete components of the glomerular capillary wall to the maintenance and regulation of permeability can be analyzed. The filtration properties of layered, intact glomeruli will be assessed in a filtration cell while the filtration across single, intact, glomerular capillary loops will be examined by confocal microscopy. In addition, confocal microscopy facilitates the investigation of intracellular calcium flux and the actin cytoskeleton, mediators of permeability in other organs, in discrete cells within intact glomeruli. This proposal is designed to investigate the function of the glomerular permeability barrier with these two novel techniques, confocal microscopy and the filtration cell. The techniques will be further characterized and then utilized to develop and expand the available isoporous and fiber matrix models of glomerular macromolecule permeability. In addition, calcium flux and the actin cytoskeleton, likely intracellular mediators of permeability, will be examined in discrete cells in intact glomeruli with confocal microscopy to determine their role in the modulation of glomerular permeability. Finally, the resultant concepts about the glomerular permeability will be applied to two pathophysiologic models associated with acute alterations in the glomerular permeability barrier.

肾小球是一个复杂的过滤器，具有非常高的水力 电导率和低大分子渗透性。 异常情况 水力传导率和大分子渗透性伴随着大多数 进行性肾病的类型，但对 肾小球通透性屏障的生理学和调节不是 发展良好，部分原因可能是缺乏模型 肾小球功能的评估可以独立于血流动力学和 荷尔蒙因素对 水和大分子穿过肾小球毛细血管的渗透性 墙。 两种肾小球通透性体外模型的开发 肾小球毛细血管壁离散成分的贡献 可以分析渗透性的维持和调节。 这 分层的、完整的肾小球的过滤特性将在 滤过细胞，同时滤过单个完整的肾小球 毛细血管袢将通过共焦显微镜检查。 此外， 共聚焦显微镜有利于细胞内的研究 钙流和肌动蛋白细胞骨架，渗透性介质 其他器官，位于完整肾小球内的离散细胞中。 该提案旨在研究肾小球的功能 共聚焦显微镜这两种新技术的渗透屏障 和过滤单元。 这些技术将得到进一步的表征 然后用于开发和扩展可用的等孔和纤维 肾小球大分子通透性矩阵模型。 此外， 钙流和肌动蛋白细胞骨架，可能是细胞内介质 渗透性，将在完整肾小球的离散细胞中进行检查 用共焦显微镜来确定它们在调节中的作用 肾小球通透性。 最后，由此产生的概念 肾小球通透性将应用于两种病理生理模型 与肾小球通透性屏障的急性改变有关。