Olson J L, Rennke H G, Venkatachalam M A
Lab Invest. 1981 Mar;44(3):271-9.
The aminonucleoside of puromycin induces proteinuria and renal damage when given to rats. Aminonucleoside of puromycin was administered to male Wistar-Furth rats as a single intravenous injection in a dose of 15 mg. per 100 gm. of body weight. The animals were studied 9 days later when the mean urinary protein was 175 mg. per 24 hours. Evidence of glomerular epithelial cell injury included massive obliteration of foot processes, appearance of microvilli, protein reabsorption droplets, extreme attenuation of cytoplasm with formation of blebs, and focal detachment of epithelial cells from glomerular basement membrane. An increase in both the amount of mesangial matrix and the number of mesangial cells was also observed. The fractional clearance (C/GFR) of anionic horseradish peroxidase had increased 18.5 times as compared to control values and was nearly equal to the C/GFR of neutral horseradish peroxidase in the experimental rats. The C/GFR of cationic horseradish peroxidase was decreased by one-third so that it approximated the C/GFRs of both anionic and neutral horseradish peroxidase. These findings indicate a nearly complete loss of the charge-selective barrier to filtration. In addition, C/GFRs of tritiated uncharged dextrans with a range of molecular radii from 18 to 58 Angstrom (A) were determined. The C/GFRs of dextrans (alpha e less than 30 A) were decreased in the experimental rats as compared to C/GFRs of dextrans of corresponding molecular size in control rats. However, the C/GFRs of dextrans (alpha e greater than 38A) were increased in experimental as compared to control rats. Further, both anionic and cationic ferritin (alpha e = 61 A) were observed in the urinary space near denuded areas of glomerular basement membrane. These results indicate that the size-selective properties of the glomerular barrier to filtration have been modified with decreased C/GFR of small molecules and increased C/GFR of large molecules. Thus, the proteinuria of aminonucleoside nephrosis in rats occurs secondary to alterations in both the charge- and size-selective barriers to glomerular filtration.
给大鼠注射嘌呤霉素氨基核苷会导致蛋白尿和肾损伤。将嘌呤霉素氨基核苷以每100克体重15毫克的剂量单次静脉注射给雄性Wistar-Furth大鼠。9天后对动物进行研究，此时平均尿蛋白为每24小时175毫克。肾小球上皮细胞损伤的证据包括足突大量消失、微绒毛出现、蛋白重吸收滴、细胞质极度变薄形成泡以及上皮细胞与肾小球基底膜局灶性脱离。还观察到系膜基质数量和系膜细胞数量增加。与对照值相比，阴离子辣根过氧化物酶的分数清除率（C/GFR）增加了18.5倍，并且在实验大鼠中几乎等于中性辣根过氧化物酶的C/GFR。阳离子辣根过氧化物酶的C/GFR降低了三分之一，使其接近阴离子和中性辣根过氧化物酶的C/GFR。这些发现表明滤过电荷选择性屏障几乎完全丧失。此外，还测定了分子半径范围为18至58埃（A）的氚标记不带电荷葡聚糖的C/GFR。与对照大鼠中相应分子大小葡聚糖的C/GFR相比，实验大鼠中葡聚糖（αe小于30 A）的C/GFR降低。然而，与对照大鼠相比，实验大鼠中葡聚糖（αe大于38 A）的C/GFR增加。此外，在肾小球基底膜剥脱区域附近的尿间隙中观察到阴离子和阳离子铁蛋白（αe = 61 A）。这些结果表明肾小球滤过屏障的大小选择性特性已发生改变，小分子的C/GFR降低，大分子的C/GFR增加。因此，大鼠嘌呤霉素肾病的蛋白尿继发于肾小球滤过电荷和大小选择性屏障的改变。
