Lee Chang-Joon, Gardiner Bruce S, Ngo Jennifer P, Kar Saptarshi, Evans Roger G, Smith David W
Faculty of Engineering and Mathematical Sciences, The University of Western Australia, Perth, Western Australia, Australia.
School of Engineering and Information Technology, Murdoch University, Perth, Western Australia, Australia; and.
Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F218-F236. doi: 10.1152/ajprenal.00657.2016. Epub 2017 Apr 12.
We develop a pseudo-three-dimensional model of oxygen transport for the renal cortex of the rat, incorporating both the axial and radial geometry of the preglomerular circulation and quantitative information regarding the surface areas and transport from the vasculature and renal corpuscles. The computational model was validated by simulating four sets of published experimental studies of renal oxygenation in rats. Under the control conditions, the predicted cortical tissue oxygen tension ([Formula: see text]) or microvascular oxygen tension (µPo) were within ±1 SE of the mean value observed experimentally. The predicted [Formula: see text] or µPo in response to ischemia-reperfusion injury, acute hemodilution, blockade of nitric oxide synthase, or uncoupling mitochondrial respiration, were within ±2 SE observed experimentally. We performed a sensitivity analysis of the key model parameters to assess their individual or combined impact on the predicted [Formula: see text] and µPo The model parameters analyzed were as follows: ) the major determinants of renal oxygen delivery ([Formula: see text]) (arterial blood Po, hemoglobin concentration, and renal blood flow); ) the major determinants of renal oxygen consumption (V̇o) [glomerular filtration rate (GFR) and the efficiency of oxygen utilization for sodium reabsorption (β)]; and 3) peritubular capillary surface area (PCSA). Reductions in PCSA by 50% were found to profoundly increase the sensitivity of [Formula: see text] and µPo to the major the determinants of [Formula: see text] and V̇o The increasing likelihood of hypoxia with decreasing PCSA provides a potential explanation for the increased risk of acute kidney injury in some experimental animals and for patients with chronic kidney disease.
我们构建了一个大鼠肾皮质氧转运的伪三维模型，纳入了球前循环的轴向和径向几何结构，以及有关血管系统和肾小体表面积及转运的定量信息。通过模拟四组已发表的大鼠肾氧合实验研究对该计算模型进行了验证。在对照条件下，预测的皮质组织氧张力（[公式：见正文]）或微血管氧张力（µPo）在实验观察平均值的±1个标准误差范围内。在缺血再灌注损伤、急性血液稀释、一氧化氮合酶阻断或线粒体呼吸解偶联情况下预测的[公式：见正文]或µPo在实验观察值的±2个标准误差范围内。我们对关键模型参数进行了敏感性分析，以评估它们对预测的[公式：见正文]和µPo的单独或综合影响。分析的模型参数如下：1）肾氧输送（[公式：见正文]）的主要决定因素（动脉血氧分压、血红蛋白浓度和肾血流量）；2）肾氧消耗（V̇o）的主要决定因素[肾小球滤过率（GFR）和钠重吸收的氧利用效率（β）]；以及3）肾小管周围毛细血管表面积（PCSA）。发现PCSA减少50%会显著增加[公式：见正文]和µPo对[公式：见正文]和V̇o主要决定因素的敏感性。随着PCSA降低缺氧可能性增加，这为一些实验动物和慢性肾病患者急性肾损伤风险增加提供了一个潜在解释。
