Heyman S N, Brezis M, Epstein F H, Spokes K, Silva P, Rosen S
Charles A. Dana Research Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Kidney Int. 1991 Oct;40(4):632-42. doi: 10.1038/ki.1991.255.
We evaluated the acute changes in cortical and outer medullary oxygen tension and the alterations in renal function and morphology within the first 90 minutes after the administration of indomethacin and iothalamate to anesthetized Sprague-Dawley rats. Both agents were found to produce marked and protracted outer medullary hypoxia averaging 12 +/- 4 and 9 +/- 2 mm Hg, respectively (mean +/- SE). Given together to salt depleted uninephrectomized rats they produced an early hypoxic injury localized selectively in the outer medulla. This lesion progressed from 3 +/- 1% of medullary thick ascending limbs (mTALs) at 15 minutes to 22 +/- 7% at 24 hours. Condensed "dark" cells were observed at 15 minutes, probably representing a type of early injury. Residual red cell mass, quantified in the outer medullary vasculature of perfusion-fixed kidneys and presumably reflecting stasis, was substantially increased in iothalamate treated rats. Red cell mass in the interbundle zone correlated with mTAL necrosis. Taken together, these results show an early period of medullary hypoxia, accompanied by a selective injury to mTALs in the central interbundle zone with apparent stasis. These findings contrast sharply with the ischemia-reflow pattern of renal damage and emphasize the important role of medullary hypoxia in the genesis of acute renal failure in this model.
我们评估了给麻醉的Sprague-Dawley大鼠注射吲哚美辛和碘他拉酸盐后最初90分钟内皮质和外髓质氧张力的急性变化以及肾功能和形态学的改变。发现这两种药物均会导致明显且持久的外髓质缺氧，平均分别为12±4和9±2 mmHg（平均值±标准误）。给盐缺乏的单侧肾切除大鼠同时注射这两种药物，会产生早期缺氧损伤，且选择性地局限于外髓质。这种损伤从15分钟时髓质厚升支（mTALs）的3±1%发展到24小时时的22±7%。在15分钟时观察到浓缩的“暗”细胞，可能代表一种早期损伤。在灌注固定肾脏的外髓质脉管系统中定量的残余红细胞量，推测反映了血流淤滞，在碘他拉酸盐处理的大鼠中显著增加。束间区的红细胞量与mTAL坏死相关。综上所述，这些结果显示了早期的髓质缺氧，伴有中央束间区mTALs的选择性损伤以及明显的血流淤滞。这些发现与肾损伤的缺血-再灌注模式形成鲜明对比，并强调了髓质缺氧在该模型急性肾衰竭发生中的重要作用。
