Oliver J D, Deen W M
Department of Chemical Engineering, Massachussetts Institute of Technology, Cambridge 02139.
Bull Math Biol. 1994 May;56(3):369-89. doi: 10.1007/BF02460463.
Dextran has been the most commonly employed test molecule for probing the selectivity of glomerular filtration to macromolecules of varying size. The usual theories for hindered transport of solid spheres through pores have limited utility in interpreting clearance data for dextran or other linear polymers because such polymers in solution more closely resemble random, solvent-filled coils than solid spheres. To provide a model for glomerular filtration of random-coil macromolecules, the equilibrium partitioning of random coils between cylindrical pores and bulk solution was simulated using Monte Carlo calculations, and those results were combined with a hydrodynamic theory for restricted motion of solvent-filled polymer coils in pores. The rates of transport predicted for either neutral random coils or for solid spores of the same Stokes-Einstein radius were significantly lower than observed transport rates of dextran through the glomerular capillary wall or across synthetic porous membranes. This facilitation of dextran transport was modeled by postulating weak, attractive interactions between dextran monomers and the pore wall. The random-coil model with attractive interactions, modeled using a short-range, square-well potential, was found to adequately represent dextran sieving data in normal rats. Various limitations of this approach are discussed.
葡聚糖一直是用于探究肾小球滤过对不同大小大分子选择性的最常用测试分子。关于固体球体通过孔隙的受阻传输的常见理论，在解释葡聚糖或其他线性聚合物的清除数据时实用性有限，因为溶液中的此类聚合物更类似于无规的、充满溶剂的线团，而非固体球体。为了提供一个无规线团大分子肾小球滤过的模型，使用蒙特卡罗计算模拟了无规线团在圆柱形孔隙和本体溶液之间的平衡分配，并将这些结果与溶剂填充的聚合物线团在孔隙中受限运动的流体动力学理论相结合。预测的中性无规线团或具有相同斯托克斯 - 爱因斯坦半径的固体孢子的传输速率，显著低于观察到的葡聚糖通过肾小球毛细血管壁或穿过合成多孔膜的传输速率。通过假定葡聚糖单体与孔壁之间存在弱的吸引相互作用，对这种葡聚糖传输的促进作用进行了建模。发现使用短程方阱势建模的具有吸引相互作用的无规线团模型，能够充分代表正常大鼠中的葡聚糖筛分数据。讨论了该方法的各种局限性。
