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模拟水和测试大分子跨肾小球毛细血管屏障的联合转运:通透选择性动力学

Modeling combined transport of water and test macromolecules across the glomerular capillary barrier: dynamics of the permselectivity.

作者信息

Mohamed Ehab I, de Lorenzo Antonino

机构信息

Human Physiology Division, Department of Neurosciences, Faculty of Medicine and Surgery, University of Rome Tor Vergata, Italy.

出版信息

Eur Biophys J. 2002 Jun;31(3):163-71. doi: 10.1007/s00249-001-0203-1. Epub 2002 Jan 25.

DOI:10.1007/s00249-001-0203-1
PMID:12029328
Abstract

The structure, function, and composition of the basement membrane of the glomerular capillaries of the mammalian kidney have been extensively studied, in light of the membrane's important physiological role in glomerular filtration of macromolecules and of its frequent involvement in renal diseases. An analytical mathematical model, based on the fiber matrix theory, was developed to describe the dynamics of the permselective function of the glomerular capillary barrier using mainly its hemodynamic and morphometric variables. The glomerular basement membrane was represented as a homogeneous three-dimensional meshwork of fibers of uniform length (L(f)), radius (R(f)), and packing density (N(fv)) and characterized by a local Darcy permeability (a measure of the intrinsic hydraulic conductance of the glomerular basement membrane). The model was appropriate for simulating in vivo fractional clearance data of neutral test macromolecules from an experimental rat model. We believe that the L(f) and R(f) best-fit numerical values, characterizing a glomerular basement membrane geometrical arrangement, may represent diagnostic measures for renal function in health and disease. That is, these parameters may signify new insights for the diagnosis of some human nephropathies and possibly may explain the beneficial effects and/or sites of action of some pharmacological modifiers (e.g., angiotensin converting enzyme inhibitors).

摘要

鉴于肾小球毛细血管基底膜在大分子肾小球滤过中的重要生理作用及其在肾脏疾病中的频繁参与,对哺乳动物肾脏肾小球毛细血管基底膜的结构、功能和组成进行了广泛研究。基于纤维基质理论,开发了一种分析数学模型,主要利用其血液动力学和形态测量学变量来描述肾小球毛细血管屏障的选择通透性功能动态。肾小球基底膜被表示为具有均匀长度(L(f))、半径(R(f))和堆积密度(N(fv))的纤维的均匀三维网络,并以局部达西渗透率(衡量肾小球基底膜固有水力传导率的指标)为特征。该模型适用于模拟来自实验大鼠模型的中性测试大分子的体内分数清除数据。我们认为,表征肾小球基底膜几何排列的L(f)和R(f)最佳拟合数值可能代表健康和疾病状态下肾功能的诊断指标。也就是说,这些参数可能为某些人类肾病的诊断提供新的见解,并可能解释某些药理修饰剂(如血管紧张素转换酶抑制剂)的有益作用和/或作用部位。

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Modeling combined transport of water and test macromolecules across the glomerular capillary barrier: dynamics of the permselectivity.模拟水和测试大分子跨肾小球毛细血管屏障的联合转运:通透选择性动力学
Eur Biophys J. 2002 Jun;31(3):163-71. doi: 10.1007/s00249-001-0203-1. Epub 2002 Jan 25.
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Angiotensin converting enzyme inhibition ameliorates glomerular filtration of macromolecules and water and lessens glomerular injury in the rat.血管紧张素转换酶抑制可改善大鼠大分子物质和水的肾小球滤过,并减轻肾小球损伤。
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