Bohrer M P, Baylis C, Robertson C R, Brenner B M, Troy J L, Willis W T
J Clin Invest. 1977 Jul;60(1):152-61. doi: 10.1172/JCI108751.
To investigate the mechanism(s) of increased filtration of serum proteins after glomerular injury, polydisperse samples of uncharged [(3)H]dextran (D) or anionic [(3)H]dextran sulfate (DS) were infused into 14 control and 16 puromycin aminonucleoside- (PAN) treated Munich-Wistar rats. Fractional clearances of D or DS ranging in radius from 18 to 42A were determined in these rats, together with direct measurements of the forces governing the glomerular filtration rate of water. Whole kidney and single nephron glomerular filtration rates were approximately 40% lower in PAN-treated rats, relative to controls, due mainly to a marked reduction in the glomerular capillary ultrafiltration coefficient and, to a lesser extent, to a small reduction in glomerular plasma flow rate as well. In PAN-treated rats, as in normal controls, inulin was found to permeate the glomerular capillary wall without measurable restriction, and both D and DS were shown to be neither secreted nor reabsorbed. Fractional clearances of uncharged D were reduced after PAN administration, falling significantly for effective D radii from 22 to 38A. Utilizing a theory based on macromolecular transport through pores, these results indicate that in PAN-treated rats, effective pore radius is the same as in controls, approximately 44A. In PAN nephrosis, however, the ratio of total pore surface area/pore length, a measure of pore density, is reduced to approximately one-third that of control, due very likely to a reduction in filtration surface area. In contrast to the results with uncharged D, fractional clearances of DS were found to increase after PAN administration for all DS radii studied. These results with D and DS suggest that proteinuria in PAN nephrosis is due, not to an increase in effective pore radius or number of pores, but rather to a diminution of the electrostatic barrier function of the glomerular capillary wall, thereby allowing increased passage of polyanions such as DS and albumin.
为了研究肾小球损伤后血清蛋白滤过增加的机制，将多分散的不带电荷的[³H]葡聚糖（D）或带阴离子的[³H]硫酸葡聚糖（DS）样本注入14只对照慕尼黑-威斯塔大鼠和16只经嘌呤霉素氨基核苷（PAN）处理的慕尼黑-威斯塔大鼠体内。测定了这些大鼠中半径在18至42埃之间的D或DS的分数清除率，并直接测量了控制水的肾小球滤过率的各种力量。与对照组相比，经PAN处理的大鼠的全肾和单肾单位肾小球滤过率大约低40%，这主要是由于肾小球毛细血管超滤系数显著降低，在较小程度上也是由于肾小球血浆流速略有降低。在经PAN处理的大鼠中，与正常对照组一样，发现菊粉可无明显限制地透过肾小球毛细血管壁，并且D和DS均未显示有分泌或重吸收现象。给予PAN后，不带电荷的D的分数清除率降低，对于有效D半径从22至38埃的情况，其分数清除率显著下降。利用基于大分子通过孔道转运的理论，这些结果表明，在经PAN处理的大鼠中，有效孔半径与对照组相同，约为44埃。然而，在PAN肾病中，总孔表面积/孔长度的比值（一种孔密度的度量）降低至对照组的约三分之一，这很可能是由于滤过表面积减少所致。与不带电荷的D的结果相反，发现给予PAN后，所研究的所有DS半径的DS分数清除率均增加。D和DS的这些结果表明，PAN肾病中的蛋白尿不是由于有效孔半径或孔数量增加，而是由于肾小球毛细血管壁的静电屏障功能减弱，从而使得带多阴离子的物质如DS和白蛋白的通过增加。
