Worcester E M
Department of Medicine, Department of Veterans Affairs Medical Center, Milwaukee, WI 53295, USA.
Semin Nephrol. 1996 Sep;16(5):474-86.
Urine contains substances that inhibit the nucleation, growth, aggregation, and cell attachment of crystals. These may function to protect the kidney against the possibility of pathological calcification in tubular fluid and urine, which are generally supersaturated with respect to calcium salts, thereby preventing stone formation. Effects on calcium oxalate are the best studied, and most of the inhibitory activity resides in macromolecules such as glycoproteins and glycosaminoglycans. Inhibitory proteins found in urine include nephrocalcin, Tamm-Horsfall protein, uropontin, crystal matrix protein (F1 prothrombin fragment), and uronic acid-rich protein (bikunin). Most of the molecules are anionic, with many acidic amino acid residues, frequently contain post-translational modifications such as phosphorylation and glycosylation, and appear to exert their effects by binding to calcium oxalate surface. The specific structural motifs that favor crystal binding and inhibition are not yet known. A number of the proteins are made by renal epithelial cells, whereas others gain access to the urine by glomerular filtration. In a number of cases, abnormalities of protein structure or function have been found in stone formers. It is not yet known what proportion of stone formers have an abnormality of inhibitor function.
尿液中含有抑制晶体成核、生长、聚集及细胞附着的物质。这些物质可能起到保护肾脏的作用,防止肾小管液和尿液中出现病理性钙化,因为肾小管液和尿液通常相对于钙盐处于过饱和状态,从而预防结石形成。对草酸钙的影响研究得最为充分,且大部分抑制活性存在于糖蛋白和糖胺聚糖等大分子中。尿液中发现的抑制性蛋白质包括肾钙蛋白、Tamm-Horsfall蛋白、尿桥蛋白、晶体基质蛋白(F1凝血酶原片段)和富含糖醛酸的蛋白质(比 Kunin)。大多数分子呈阴离子性,含有许多酸性氨基酸残基,经常含有磷酸化和糖基化等翻译后修饰,并且似乎通过与草酸钙表面结合发挥作用。目前尚不清楚有利于晶体结合和抑制的具体结构基序。许多蛋白质由肾上皮细胞产生,而其他一些蛋白质则通过肾小球滤过进入尿液。在许多情况下,已在结石形成者中发现蛋白质结构或功能异常。目前尚不清楚结石形成者中抑制剂功能异常的比例是多少。