Kretzler M, Koeppen-Hagemann I, Kriz W
Anatomy and Cell Biology Institute I, University of Heidelberg, Germany.
Virchows Arch. 1994;425(2):181-93. doi: 10.1007/BF00230355.
The progressive renal disease model of chronic uninephrectomy-desoxycorticosterone-trimethylacetate (UNX-DOCA) hypertension is associated with mesangial proliferation as a major disease mechanism. A detailed structural analysis of the alterations in glomerular structure which accompany the development of sclerosis in this model has not been made. Male Munich-Wistar rats underwent UNX, received weekly injections of the aldosterone agonist DOCA and 1% sodium chloride as drinking solution and were compared with sham operated controls (CON). Thirty eight days after onset, UNX animals had an albuminuria of 183 +/- 180 mg/day versus 0.38 +/- 0.22 mg/day in CON. Kidneys were fixed by total body perfusion and renal tissue processed for light and electron-microscopy. Superficial and deep total glomerular volume increased from 2.18 +/- 0.15 (deep: 2.57 +/- 0.24) 10(6) microns 3 in CON to 3.98 +/- 0.81 (deep: 3.95 +/- 0.63) 10(6) microns 3 in UNX. In addition to overall tuft hypertrophy, structural analysis revealed severe destruction of tuft architecture with mesangial expansion and/or capillary ballooning, leading to local tuft enlargements. Podocytes overlying the expanded areas appeared unable to adapt to cover the increased tuft surfaces. They developed severe lesions in cell architecture leading to denudation of glomerular basement membrane (GBM)-areas. "Naked" GBM appears to represent a nidus for hyalinosis, thrombosis and synechia formation, which progresses to segmental sclerosis. In the UNX-DOCA model of chronic glomerular hypertension local mesangial expansion was frequently encountered but no evidence was found that mesangial proliferation and matrix production proceeded to sclerosis. The crucial damage to the glomerulus in this model would appear to be attributable to podocyte failure, with the resultant GBM denudation triggering synechia formation, hyalinosis and ultimately glomerulosclerosis.
慢性单肾切除-脱氧皮质酮-三甲基乙酸（UNX-DOCA）高血压的进行性肾病模型与系膜增殖相关，这是主要的疾病机制。尚未对该模型中伴随硬化发展的肾小球结构改变进行详细的结构分析。雄性慕尼黑-威斯塔大鼠接受了单肾切除术，每周注射醛固酮激动剂DOCA，并饮用1%的氯化钠溶液，与假手术对照组（CON）进行比较。发病38天后，UNX组动物的蛋白尿为183±180mg/天，而CON组为0.38±0.22mg/天。通过全身灌注固定肾脏，并对肾组织进行光镜和电镜处理。浅表和深部肾小球总体积从CON组的2.18±0.15（深部：2.57±0.24）×10⁶μm³增加到UNX组的3.98±0.81（深部：3.95±0.63）×10⁶μm³。除了整体的肾小球丛肥大外，结构分析显示肾小球丛结构严重破坏，伴有系膜扩张和/或毛细血管球样变，导致局部肾小球丛增大。覆盖在扩张区域的足细胞似乎无法适应以覆盖增加的肾小球丛表面。它们的细胞结构出现严重病变，导致肾小球基底膜（GBM）区域裸露。“裸露”的GBM似乎是透明变性、血栓形成和粘连形成的病灶，进而发展为节段性硬化。在慢性肾小球高血压的UNX-DOCA模型中，经常遇到局部系膜扩张，但未发现系膜增殖和基质产生发展为硬化的证据。该模型中对肾小球的关键损害似乎归因于足细胞功能障碍，由此产生的GBM裸露引发粘连形成、透明变性，最终导致肾小球硬化。
