Schwartz M M, Bidani A K, Lewis E J
Lab Invest. 1986 Dec;55(6):673-9.
The pathogenesis of glomerular scarring in proteinuric diseases is unknown, but glomerular epithelial cell (GEC) injury has been implied by the glomerular pathology seen in patients with focal segmental glomerular sclerosis and the nephrotic syndrome. We studied the effect of proteinuria on glomerular histology and GEC structure and function in rats made proteinuric for up to 8 weeks by the daily parenteral injection of homologous serum albumin. Proteinuria in the albumin-injected rats peaked at a mean level of 131 +/- 12 mg/24 hours (mean +/- SD) during the 1st week. It subsequently plateaued at 41 +/- 6 mg/24 hours but remained significantly greater than the saline-injected controls throughout the study. The albumin-injected rats developed slight but significant increases in blood pressure, serum albumin, plasma volume, and urine urea nitrogen compared to the saline injected controls. The serum creatinine was not different from controls. In the albumin-injected rats no glomerular scarring was observed after 8 weeks of proteinuria. The GEC developed albumin reabsorption droplets and signs of activity including increased numbers of organelles, vacuoles, and cytoplasmic hypertrophy, but there were no signs of irreversible GEC damage. The GEC foot processes were quantitated morphometrically, and there was no evidence of effacement after eight 4 or 8 weeks of proteinuria. GEC endocytic function, evaluated by the technique of protamine heparin aggregate disappearance, was not different from the saline injected controls. Proteinuria caused by the chronic administration of homologous serum albumin for 8 weeks is regularly associated with increased blood pressure, plasma volume, and serum albumin and ultrastructural changes in the GEC. These morphologic changes in the GEC apparently represent a normal response to proteinuria and are not evidence for irreversible cell damage. Despite their avid endocytosis of filtered plasma proteins, GEC endocytic function remains normal. These experimental results imply that glomerular sclerosis is not a consequence of proteinuria per se.
蛋白尿性疾病中肾小球瘢痕形成的发病机制尚不清楚，但局灶节段性肾小球硬化症和肾病综合征患者的肾小球病理表现提示肾小球上皮细胞（GEC）损伤。我们通过每日经皮下注射同源血清白蛋白使大鼠蛋白尿长达8周，研究了蛋白尿对肾小球组织学以及GEC结构和功能的影响。注射白蛋白的大鼠蛋白尿在第1周达到峰值，平均水平为131±12mg/24小时（平均值±标准差）。随后稳定在41±6mg/24小时，但在整个研究过程中仍显著高于注射生理盐水的对照组。与注射生理盐水的对照组相比，注射白蛋白的大鼠血压、血清白蛋白、血浆容量和尿尿素氮略有但显著升高。血清肌酐与对照组无差异。蛋白尿8周后，注射白蛋白的大鼠未观察到肾小球瘢痕形成。GEC出现白蛋白重吸收滴和活性迹象，包括细胞器、空泡数量增加和细胞质肥大，但没有不可逆GEC损伤的迹象。通过形态计量学对GEC足突进行定量，蛋白尿4周或8周后没有足突消失的证据。通过鱼精蛋白肝素聚集体消失技术评估的GEC内吞功能与注射生理盐水的对照组无差异。慢性给予同源血清白蛋白8周引起的蛋白尿常伴有血压、血浆容量和血清白蛋白升高以及GEC超微结构改变。GEC的这些形态学变化显然代表了对蛋白尿的正常反应，并非不可逆细胞损伤的证据。尽管GEC对滤过的血浆蛋白有强烈的内吞作用，但其内吞功能仍保持正常。这些实验结果表明肾小球硬化不是蛋白尿本身的后果。
