Keane W F, Raij L
Lab Invest. 1985 Jun;52(6):599-604.
Clinical and experimental studies suggest that accumulation of phlogogenic macromolecules in the glomerular mesangium may lead to mesangial expansion and eventual glomerulosclerosis. In focal glomerulosclerosis and nephrotic syndrome entrapment of macromolecules is observed in areas of glomerulosclerosis. To determine whether mesangial uptake of radiolabeled, heat-aggregated IgG (AG125I), a biologically active macromolecular protein, is influenced by increased glomerular filtration barrier permeability, we evaluated the glomerular uptake of AG125I in three models of proteinuria: aminonucleoside of puromycin nephropathy (PAN), adriamycin nephropathy, and Heyman's nephropathy. Rats were studied approximately 1 week after onset of proteinuria. AG125I was measured in preparations of isolated glomeruli and compared to simultaneous blood, liver, and spleen levels. Only rats with PAN had a marked increase in glomerular AG125I compared to control rats, 7.8 versus 2.6 micrograms/mg of glomeruli, respectively. We then evaluated whether a continuous infusion of a competitive inhibitor of angiotensin II, saralasin (300 micrograms/kg of body weight/minute), influenced mesangial uptake of AG125I in PAN rats. Strikingly, glomerular AG125I in rats with PAN was reduced to levels comparable to that observed in control rats infused with only saralasin, 2.8 versus 3.0 micrograms/mg of glomeruli, respectively. This effect on glomerular AG125I content was independent of any significant effect of saralasin on blood, hepatic, or splenic levels of AG125I. Moreover, these changes in glomerular AG125I in saralasin-infused rats with PAN did not appear to directly correlate with changes in whole kidney function. These studies also demonstrated that proteinuria per se did not influence mesangial uptake of macromolecules. Thus, these data indicated that angiotensin II had an important effect on intraglomerular factors that modulate mesangial localization of phlogogenic macromolecules.
临床和实验研究表明，促炎大分子在肾小球系膜中的蓄积可能导致系膜扩张并最终发展为肾小球硬化。在局灶性肾小球硬化和肾病综合征中，在肾小球硬化区域可观察到大分子的截留。为了确定放射性标记的热聚集IgG（AG125I，一种生物活性大分子蛋白）的系膜摄取是否受肾小球滤过屏障通透性增加的影响，我们在三种蛋白尿模型中评估了AG125I的肾小球摄取：嘌呤霉素肾病（PAN）的氨基核苷、阿霉素肾病和海曼氏肾病。在蛋白尿发作后约1周对大鼠进行研究。在分离的肾小球制剂中测量AG125I，并与同时期的血液、肝脏和脾脏水平进行比较。与对照大鼠相比，只有PAN大鼠的肾小球AG125I显著增加，分别为7.8微克/毫克肾小球和2.6微克/毫克肾小球。然后我们评估了持续输注血管紧张素II的竞争性抑制剂沙拉新（300微克/千克体重/分钟）是否会影响PAN大鼠系膜对AG125I的摄取。令人惊讶的是，PAN大鼠的肾小球AG125I降至与仅输注沙拉新的对照大鼠相当的水平，分别为2.8微克/毫克肾小球和3.0微克/毫克肾小球。这种对肾小球AG125I含量的影响与沙拉新对血液、肝脏或脾脏中AG125I水平的任何显著影响无关。此外，输注沙拉新的PAN大鼠肾小球AG125I的这些变化似乎与全肾功能的变化没有直接相关性。这些研究还表明，蛋白尿本身并不影响大分子的系膜摄取。因此，这些数据表明血管紧张素II对调节促炎大分子系膜定位的肾小球内因素有重要影响。
