Simulations of increased glomerular capillary wall strain in the 5/6-nephrectomized rat.
Simulations of increased glomerular capillary wall strain in the 5/6-nephrectomized rat.
复制标题
5/6-否切除大鼠中肾小球毛细血管壁应变增加的模拟。
DOI：
10.1111/micc.12721
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发表时间：
2021-10
期刊：
影响因子：
2.4
通讯作者：
Navar, L. Gabriel
中科院分区：
文献类型：
--
作者：
Richfield, Owen;Cortez, Ricardo;Navar, L. Gabriel
慢性肾小球高血压与肾小球损伤和硬化有关;然而，压力增加损害肾小球足细胞的机制仍不清楚。我们检验了肾小球压力增加可能通过增加肾小球毛细血管壁的应变而不利地影响足细胞结构完整性的假设，并且肾小球毛细血管壁应变可能在与肾小球高血压相关的疾病状态中肾小球损伤的持续中起重要作用。我们开发了一种符合解剖学的精确数学模型，用于对5/6肾切除慢性肾病大鼠模型的残余肾小球中肾小球毛细血管壁的应变进行量化。在估计肾小球毛细血管中的机械应力和应变方面，该数学模型是对先前模型的实质性改进，先前模型不考虑压力引起的肾小球毛细血管直径在整个网络中分布血浆和红细胞的变化。使用先前报道的测量肾小球体积变化作为灌注压函数的实验数据，我们估计了对照和5/6肾切除条件下肾小球毛细血管壁的杨氏模量。我们发现，在5/6肾切除条件下，杨氏模量从对照条件下的7.8 MPa增加到8.6 MPa，但由于基线肾小球毛细血管直径增加了23.3%，毛细血管的顺应性在5/6肾切除条件下增加。我们发现，在5/6肾切除条件下，肾小球毛细血管壁应变比对照组增加约3倍，这可能会对系膜细胞和足细胞产生不利影响。5/6肾切除条件的模型模拟中的应变大小与体外引起足细胞肥大和肌动蛋白细胞骨架重组的应变大小一致。我们的研究结果表明，肾小球毛细血管壁应变可能会直接有害地影响足细胞，以及与其他机械变化和环境因素固有的在体内设置，以加强肾小球损伤在严重的肾功能衰竭的条件。
Chronic glomerular hypertension is associated with glomerular injury and sclerosis; however, the mechanism by which increases in pressure damage glomerular podocytes remains unclear. We tested the hypothesis that increases in glomerular pressure may deleteriously affect podocyte structural integrity by increasing the strain of the glomerular capillary walls, and that glomerular capillary wall strain may play a significant role in the perpetuation of glomerular injury in disease states that are associated with glomerular hypertension. We developed an anatomically accurate mathematical model of a compliant, filtering rat glomerulus to quantify the strain of the glomerular capillary walls in a remnant glomerulus of the 5/6‐nephrectomized rat model of chronic kidney disease. In terms of estimating the mechanical stresses and strains in the glomerular capillaries, this mathematical model is a substantial improvement over previous models which do not consider pressure‐induced alterations in glomerular capillary diameters in distributing plasma and erythrocytes throughout the network. Using previously reported data from experiments measuring the change of glomerular volume as a function of perfusion pressure, we estimated the Young's modulus of the glomerular capillary walls in both control and 5/6‐nephrectomized conditions. We found that in 5/6‐nephrectomized conditions, the Young's modulus increased to 8.6 MPa from 7.8 MPa in control conditions, but the compliance of the capillaries increased in 5/6‐nephrectomized conditions due to a 23.3% increase in the baseline glomerular capillary diameters. We found that glomerular capillary wall strain was increased approximately threefold in 5/6‐nephrectomized conditions over control, which may deleteriously affect both mesangial cells and podocytes. The magnitudes of strain in model simulations of 5/6‐nephrectomized conditions were consistent with magnitudes of strain that elicit podocyte hypertrophy and actin cytoskeleton reorganization in vitro. Our findings indicate that glomerular capillary wall strain may deleteriously affect podocytes directly, as well as act in concert with other mechanical changes and environmental factors inherent to the in vivo setting to potentiate glomerular injury in severe renoprival conditions.
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DOI：
10.1152/ajprenal.90423.2008
发表时间：
2010-02-01
影响因子：
4.2
作者：
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影响因子：
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DOI：
10.1115/1.4007098
发表时间：
2012-08-01
影响因子：
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作者：
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