Podocyte injury underlies the progression of focal segmental glomerulosclerosis in the fa/fa Zucker rat
Podocyte injury underlies the progression of focal segmental glomerulosclerosis in the fa/fa Zucker rat
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DOI：
10.1046/j.1523-1755.2001.00777.x
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发表时间：
2001-07-01
影响因子：
19.6
通讯作者：
Gretz, N
中科院分区：
文献类型：
--
作者：
Gassler, N;Elger, M;Gretz, N
背景糖尿病肾病进展为慢性肾衰竭是基于活性肾单位的进行性丧失。糖尿病肾病中肾单位退化的方式以及损伤是否可以从肾单位转移到肾单位，尚不清楚。我们研究了Zucker大鼠的肾单位变性。它被认为是非胰岛素依赖型糖尿病的模型。通过先进的形态学技术，包括连续切片，对肾功能下降的Wistar大鼠和fal+对照大鼠的肾脏进行结构分析。高分辨率光学显微镜，透射电子显微镜。细胞化学和免疫组织此外，还进行了铁蛋白的示踪研究。退化过程始于肾小球，足细胞受损。包括足突消失假囊肿形成和溶酶体颗粒和脂滴的细胞质积聚。肾单位的变性遵循丛粘连介导的途径，从毛细血管的错误过滤包括在粘附到肾小球。其次是围绕整个肾小球的肾小球旁间隙的形成。以及通过肾小球管连接。这种机制似乎在节段性肾小球损伤进展为整体硬化以及相应小管的变性中起主要作用。在此过程中，肾单位经历变性的方式确保了破坏性影响仅限于最初受影响的肾单位。没有证据表明疾病在肾小管上皮水平从一个肾单位转移到另一个肾单位。进入这一退化途径的每个肾单位似乎分别从肾小球的相同初始损伤开始。
Background. The progression of diabetic nephropathy to chronic renal failure is based on the progressive loss of viable nephrons. The manner in which nephrons degenerate in diabetic nephropathy and whether the injury could be transferred from nephron to nephron art: insufficiently understood. We studied nephron degeneration in the falfa Zucker rat. which is considered to be a model for non-insulin-dependent diabetesMethods. Kidneys of falfa rats with an established decline of renal function and of fal+ controls were structurally analyzed by advanced morphological techniques, including serial sectioning. high resolution light microscopy, transmission electron microscopy. cytochemistry. and immunohistochemistry. In addition, tracer studies with ferritin were performed.Results. The degenerative process started in the glomerulus with damage to podocytes. including foot process effacement. pseudocyst formation, and cytoplasmic accumulation of lysosomal granules and lipid droplets. The degeneration of the nephron followed the tuft adhesion-mediated pathway with misdirected filtration from capillaries included in the adhesion toward the interstitium. This was Followed by the formation of paraglomerular spaces that extended around the entire glomerulus. as well as via the glomerulotubular junction. to the corresponding tubulointerstitium This mechanism appeared to play a major role in the progression of the segmental glomerular injury to global sclerosis as well as to the degeneration of the corresponding tubule.Conclusions. The way a nephron undergoes degeneration in this process assures that the destructive effects remain confined to the initially affected nephron. No evidence for a transfer of the disease from nephron to nephron at the level of the tubulointerstitium was found. Thus. each nephron entering this pathway to degeneration appears to start separately with the same initial injuries at the glomerulus.