Shanley P F, Brezis M, Spokes K, Silva P, Epstein F H, Rosen S
Kidney Int. 1986 May;29(5):1033-7. doi: 10.1038/ki.1986.103.
Two distinct types of injury, cytoplasmic edema and cell fragmentation occur in the S3 segment of the proximal tubule in isolated hypoxic perfused rat kidneys (Krebs-albumin medium gassed without O2). The proportion of S3 tubules with fragmentation strongly correlated with the GFR and urine output during the perfusion, and approached 100% when the GFR was increased by high perfusion pressure. Conversely, the fragmentation lesion was absent and the edema lesion extensive when tubular transport was inhibited by perfusion with hyperoncotic medium to prevent glomerular filtration or by addition of ouabain (10(-2) M) to the perfusate. Polyene antibiotics increase membrane permeability and thus the work of active electrolyte transport. Perfusion with amphotericin (3 X 10(-5) M) or nystatin (200 U/mliter) in oxygenated medium also produced fragmentation in S3. The lesion was prevented in the non-filtering kidney. Ouabain completely eliminated the cell fragmentation due to nystatin and significantly reduced that due to amphotericin. These results suggest that the injury of cell fragmentation is enhanced by transport activity and diminished when transport is inhibited. The edema lesion appears fundamentally different and more akin to lesions described in ischemia where tubular flow is absent, active transport is diminished, and the morphologic changes appear related to loss of cell volume regulation. The type of hypoxic damage exhibited by proximal tubular S3 segments may therefore be conditioned by active ion transport of tubular cells.
在离体缺氧灌注的大鼠肾脏（用无氧气体置换的克雷布斯白蛋白培养基）中，近端小管S3段会出现两种不同类型的损伤，即细胞质水肿和细胞破碎。S3段出现破碎的比例与灌注期间的肾小球滤过率（GFR）和尿量密切相关，当通过高灌注压力使GFR升高时，该比例接近100%。相反，当用高渗培养基灌注以防止肾小球滤过或在灌注液中加入哇巴因（10⁻²M）抑制肾小管转运时，破碎损伤消失，水肿损伤广泛。多烯抗生素会增加膜通透性，从而增加主动电解质转运的工作量。在含氧培养基中用两性霉素（3×10⁻⁵M）或制霉菌素（200U/升）灌注也会在S3段产生破碎。在无滤过功能的肾脏中可预防这种损伤。哇巴因完全消除了制霉菌素引起的细胞破碎，并显著减少了两性霉素引起的细胞破碎。这些结果表明，细胞破碎损伤因转运活性而增强，在转运受抑制时则减弱。水肿损伤似乎有根本不同，更类似于缺血时所描述的损伤，即肾小管无血流、主动转运减弱，形态学变化似乎与细胞体积调节丧失有关。因此，近端小管S3段所表现出的缺氧损伤类型可能受肾小管细胞主动离子转运的影响。
