SUPERCOMPUTER SIMULATION OF THE MAMMALIAN KIDNEY

这项工作的总体目标是在 膜和分子水平的预测数学模型 哺乳动物的肾脏，对了解其正常和 功能受损。本报告中提出的研究的总体目的 应用程序是第一次开发出一个数学模型 哺乳动物的肾脏，结合了逼真的建筑，细胞和 水和溶质的细胞旁运输，以及溶质和 血浆和红细胞之间的水。这一发展是建立在 更简单的模型，但需要向量和并行处理 超级计算机的能力。超级计算机模型的发展 将分几个阶段进行： 1.近端小管、粗大升支、皮质的详细模型 集合管和集合管，包括细胞和集合管 细胞旁途径和下列变量：Na，K，H，NH4，Cl-， HCO3-、HPO4-、H2PO42-、葡萄糖、尿素、静水压力、电性 潜力和体积流将被纳入中央核心模型 在这一阶段，我们的主要数学目标是 优化向量Fortran代码。从生理上讲，这种模式将被使用 分析皮质微穿刺点数据，特别是关于钠和 K处理。 2.一种多核电解质肾脏中心核模型。 Henle但不太详细的管状模型中环的长度分布 将用于优化并行代码。该模型将应用于 了解渗透分子在体内产生的可能作用 髓内浓缩机构。它还将用于模拟 肾脏从利尿过渡到抗利尿。 3.多管模型将通过纳入 详细的肾小管模型和详细的肾小管髓质结构 和血管。随着越来越详细的模型，它将是 可模拟虚拟靶标对整体功能的影响 药物和激素对膜转运的作用。 4.红细胞和血浆之间的溶质和水的交换将 添加到模型中。

The overall goal of this work is to synthesize experimental data at the membrane and molecular level into predictive mathematical models of the mammalian kidney that are useful in understanding both its normal and diseased function. The general purpose of the research proposed in this application is to develop for the first time a mathematical model of the mammalian kidney that combines a realistic architecture, cellular and paracellular transport of water and solutes, and exchange of solutes and water between plasma and red blood cells. This development builds on simpler models, but requires the vector and parallel processing capabilities of supercomputers. Development of the supercomputer models will proceed in several stages: 1. Detailed models of proximal tubule, thick ascending limb, cortical collecting tubule, and collecting duct, which include both cellular and paracellular pathways and the following variables: Na+, K+, H+, NH4+, Cl-, HCO3-, HPO4-,H2PO42-, glucose, urea, hydrostatic pressure, electric potential, and volume flow will be incorporated into a central core model of a cortical nephron In this phase our primary mathematical aim will be to optimize the vector Fortran code. Physiologically this model will be used to analyze cortical micropuncture data, particularly with respect to Na and K handling. 2. A multinephron electrolyte central core model of the kidney with a distribution of lengths of loops of Henle but less detailed tubular models will be used to optimize parallel code. This model will be applied to understanding the possible role of osmolyte production in the inner medullary concentrating mechanism. It will also be used to simulate the transition of the kidney from diuresis to antidiuresis. 3. The multinephron model will evolve further by incorporation of the detailed tubular models, and the detailed medullary architecture of tubules and blood vessels. With progressively more detailed models it will be possible to simulate the effect on overall function of hypothesized target actions of drugs and hormones on membrane transport. 4. Exchange of solutes and water between red blood cells and plasma will be added to the model.