GLOMERULAR SIEVING OF ANIONIC AND NEUTRAL BOVINE ALBUMINS IN PROTEINURIC RATS
GLOMERULAR SIEVING OF ANIONIC AND NEUTRAL BOVINE ALBUMINS IN PROTEINURIC RATS
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DOI：
10.1038/ki.1985.153
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发表时间：
1985-01-01
影响因子：
19.6
通讯作者：
HUNSICKER, LG
中科院分区：
文献类型：
--
作者：
BERTOLATUS, JA;HUNSICKER, LG
目的：研究大鼠急性经己二甲双胍（HDM）或慢性经阿霉素（ADM）肾病模型肾小球通透性缺陷导致蛋白尿的特点（阿霉素）（Adira），我们开发并验证了一种组织蓄积法，用于同时测定阴离子131 I标记的牛白蛋白的肾小球筛分系数（GSC（BSA-pI 4.9）和125 I标记的电荷修饰的中性BSA（nBSA-pI 7.5至8.0）。通过将尿液中排泄的标记物与过滤但被肾小管重吸收的标记物相加，计算总过滤标记物。后者通过从右滤过肾内累积的总标记物中减去左肾中存在的间质标记物来确定，左肾在甘露醇利尿期间通过输尿管结扎而变得非滤过。实验表明，在清除研究期间，标记物循环并完整排泄，既不降解也不脱碘。在对照动物中，nBSA的GSC（0.026 . ±. 0.004）大大超过BSA（0.0006 ±. 0.0002），证明了磁导率的正常电荷依赖性。两个蛋白尿组的BSA GSC均显着增加（HDM：0.021。±。0.005;阿德里亚：0.025。0.004），这与尿液中大鼠白蛋白的出现相关。HDM大鼠的nBSA的GSC也有两倍的增加（0.049 ± 0.0001）。0.005），表明渗透率的尺寸依赖性的改变。BSA和nBSA的GSC的绝对增加是相似的，这表明白蛋白尿是由于肾小球滤器中出现新的“孔”引起的，这些孔对白蛋白大小的蛋白质没有电荷选择性。因此，输注HDM（其结合并中和GBM阴离子）似乎通过诱导肾小球滤过器的结构变化而产生白蛋白尿。相反，Adria大鼠的nBSA的GSC没有显著增加（0.031 ± 0.031）。0.005），表明白蛋白大小的蛋白质的大小依赖性或渗透性没有显著变化。在这些动物中，阴离子BSA的GSC接近中性nBSA的GSC，表明阿霉素通过显着降低渗透性的正常电荷依赖性来诱导蛋白尿。
To characterize the defect in glomerular permeability leading to albuminuria in rats made nephrotic acutely by infusion of hexadimethrine (HDM) or chronically by administration of Adriamycin (doxorubicin) (Adira), we developed and validated a tissue accumulation method for simultaneous determination of the glomerular sieving coefficients (GSC) of anionic 131I-labeled bovine albumin (BSA-pI 4.9) and 125I-labeled charge-modified neutral BSA (nBSA-pI 7.5 to 8.0). Total filtered marker was calculated by adding marker excreted in the urine to that filtered but reabsorbed by the tubules. The latter was determined by subtracting interstitial marker present in the left kidney, rendered non-filtering by ureteral ligation during mannitol diuresis, from the total marker accumulating within the right, filtering kidney. Experiments showed that markers circulated and were excreted intact and were neither degraded nor deiodinated during the period of the clearance studies. In control animals the GSC of nBSA (0.026 .+-. 0.004) greatly exceeded that of BSA (0.0006 .+-. 0.0002), demonstrating the normal charge dependence of permeability. Both proteinuric groups had marked increases in the GSC of BSA (HDM: 0.021 .+-. 0.005; Adria: 0.025 .+-. 0.004), which correlated with appearance of rat albumin in their urine. HDM rats also had a twofold increase in the GSC of nBSA (0.049 .+-. 0.005), indicating alteration of the size dependence of permeability. The absolute increase of GSC of BSA and nBSA was similar, suggesting that albuminuria resulted from appearance of new "pores" in the glomerular filter that were not charge selective for proteins of the size of albumin. Thus, infusion of HDM, which binds to and neutralizes GBM anions, appears to produce albuminuria by inducing a structural change in the glomerular filter. Conversely, Adria rats had no significant increase in the GSC of nBSA (0.031 .+-. 0.005), indicating no significant change in the size dependence or permeability for proteins of the size of albumin. In these animals, the GSC of the anionic BSA approached that of the neutral nBSA, indicating that Adriamycin indcues albuminuria by markedly reducing the normal charge dependence of permeability.