Carvalho M, Mulinari R A, Nakagawa Y
Kidney Stone Program, Division of Biological Sciences and the Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.
Braz J Med Biol Res. 2002 Oct;35(10):1165-72. doi: 10.1590/s0100-879x2002001000009. Epub 2002 Oct 13.
One of the defenses against nephrolithiasis is provided by macromolecules that modulate the nucleation, growth, aggregation and retention of crystals in the kidneys. The aim of the present study was to determine the behavior of two of these proteins, Tamm-Horsfall and uromodulin, in calcium oxalate crystallization in vitro. We studied a group of 10 male stone formers who had formed at least one kidney stone composed of calcium oxalate. They were classified as having idiopathic nephrolithiasis and had no well-known metabolic risk factors involved in kidney stone pathogenesis. Ten normal men were used as controls, as was a group consisting of five normal women and another consisting of five pregnant women. Crystallization was induced by a fixed supersaturation of calcium oxalate and measured with a Coulter Counter. All findings were confirmed by light and scanning electron microscopy. The number of particulate material deposited from patients with Tamm-Horsfall protein was higher than that of the controls (P<0.001). However, Tamm-Horsfall protein decreased the particle diameter of the stone formers when analyzed by the mode of the volume distribution curve (P<0.002) (5.64 +/- 0.55 microm compared to 11.41 +/- 0.48 microm of uromodulin; 15.94 +/- 3.93 microm and 12.45 +/- 0.97 microm of normal men Tamm-Horsfall protein and uromodulin, respectively; 8.17 +/- 1.57 microm and 9.82 +/- 0.95 microm of normal women Tamm-Horsfall protein and uromodulin, respectively; 12.17 +/- 1.41 m and 12.99 +/- 0.51 microm of pregnant Tamm-Horsfall protein and uromodulin, respectively). Uromodulin produced fewer particles than Tamm-Horsfall protein in all groups. Nonetheless, the total volume of the crystals produced by uromodulin was higher than that produced by Tamm-Horsfall protein. Our results indicate a different effect of Tamm-Horsfall protein and uromodulin. This dual behavior suggests different functions. Tamm-Horsfall protein may act on nucleation and inhibit crystal aggregation, while uromodulin may promote aggregation of calcium oxalate crystals.
肾脏中的大分子物质可对肾结石起到一定的防御作用，它们能够调节晶体在肾脏中的成核、生长、聚集和潴留。本研究旨在确定其中两种蛋白质，即Tamm-Horsfall蛋白和尿调节蛋白，在草酸钙体外结晶过程中的行为表现。我们研究了一组10名男性结石形成者，他们至少形成过一块由草酸钙组成的肾结石。他们被归类为特发性肾结石患者，且不存在已知的与肾结石发病机制相关的代谢风险因素。选取10名正常男性作为对照，另外还有一组由5名正常女性组成的对照组以及一组由5名孕妇组成的对照组。通过固定的草酸钙过饱和度诱导结晶，并使用库尔特计数器进行测量。所有结果均通过光学显微镜和扫描电子显微镜得到证实。含有Tamm-Horsfall蛋白的患者所沉积的颗粒物质数量高于对照组（P<0.001）。然而，当通过体积分布曲线的模式进行分析时，Tamm-Horsfall蛋白减小了结石形成者的颗粒直径（P<0.002）（与尿调节蛋白的11.41±0.48微米相比为5.64±0.55微米；正常男性的Tamm-Horsfall蛋白和尿调节蛋白分别为15.94±3.93微米和12.45±0.97微米；正常女性的Tamm-Horsfall蛋白和尿调节蛋白分别为8.17±1.57微米和9.82±0.95微米；孕妇的Tamm-Horsfall蛋白和尿调节蛋白分别为12.17±1.41微米和12.99±0.51微米）。在所有组中，尿调节蛋白产生的颗粒比Tamm-Horsfall蛋白少。尽管如此，尿调节蛋白产生的晶体总体积高于Tamm-Horsfall蛋白产生的晶体总体积。我们的结果表明Tamm-Horsfall蛋白和尿调节蛋白具有不同的作用效果。这种双重行为提示了它们具有不同的功能。Tamm-Horsfall蛋白可能作用于成核过程并抑制晶体聚集，而尿调节蛋白可能促进草酸钙晶体的聚集。
