Bohrer M P, Baylis C, Humes H D, Glassock R J, Robertson C R, Brenner B M
J Clin Invest. 1978 Jan;61(1):72-8. doi: 10.1172/JCI108927.
To examine the electrostatic effects of fixed negative charges on the glomerular capillary wall, polydisperse [(3)H]DEAE dextran, a polycationic form of dextran, was infused into 10 Munich-Wistar rats. Fractional clearances of DEAE ranging in radius from 18 to 44A were determined in these rats, together with direct measurements of the forces and flows governing the glomerular filtration rate of water. These results were compared with data previously obtained in Munich-Wistar rats receiving tritiated neutral dextran (D) and polyanionic dextran sulfate (DS). Measured values for the determinants of the glomerular filtration rate of water in rats given DEAE were found to be essentially identical to those in rats given either D or DS. In addition, DEAE was shown to be neither secreted nor reabsorbed. Fractional clearances of polycationic DEAE were increased relative to both D and DS, the increase relative to D being significant for effective molecular radii ranging from 24 to 44A. Fractional DEAE clearances were also measured in a separate group of six Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). Fractional DEAE clearances in NSN rats were reduced significantly, relative to values measured in normal rats, for effective DEAE radii ranging from 18 to 42A. Moreover, in NSN rats, fixed negative charges on the glomerular capillary wall were greatly reduced, relative to non-NSN rats, as evidenced by a reduction in intensity of colloidal iron staining. Thus, in NSN rats, DEAE clearances were essentially indistinguishable from values obtained with both neutral D and polyanionic DS.
为了研究肾小球毛细血管壁上固定负电荷的静电效应,将多分散的[³H]二乙氨基乙基葡聚糖(一种葡聚糖的聚阳离子形式)注入10只慕尼黑-威斯塔大鼠体内。测定了这些大鼠体内半径在18至44埃之间的二乙氨基乙基葡聚糖的分数清除率,并直接测量了控制水的肾小球滤过率的力和流量。将这些结果与先前在接受氚标记中性葡聚糖(D)和聚阴离子硫酸葡聚糖(DS)的慕尼黑-威斯塔大鼠中获得的数据进行了比较。发现给予二乙氨基乙基葡聚糖的大鼠中,水的肾小球滤过率决定因素的测量值与给予D或DS的大鼠中的测量值基本相同。此外,二乙氨基乙基葡聚糖既不分泌也不重吸收。聚阳离子二乙氨基乙基葡聚糖的分数清除率相对于D和DS均有所增加,对于有效分子半径在24至44埃之间的情况,相对于D的增加具有显著性。还在另一组6只处于肾毒性血清肾炎(NSN)自体早期阶段的慕尼黑-威斯塔大鼠中测量了二乙氨基乙基葡聚糖的分数清除率。对于有效二乙氨基乙基葡聚糖半径在18至42埃之间的情况,NSN大鼠中的二乙氨基乙基葡聚糖分数清除率相对于正常大鼠中测量的值显著降低。此外,在NSN大鼠中,肾小球毛细血管壁上的固定负电荷相对于非NSN大鼠大大减少,这通过胶体铁染色强度的降低得以证明。因此,在NSN大鼠中,二乙氨基乙基葡聚糖的清除率与用中性D和聚阴离子DS获得的值基本无法区分。