ACUTE RENAL-FAILURE WITH SELECTIVE MEDULLARY INJURY IN THE RAT
ACUTE RENAL-FAILURE WITH SELECTIVE MEDULLARY INJURY IN THE RAT
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DOI：
10.1172/jci113612
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发表时间：
1988-08-01
影响因子：
15.9
通讯作者：
ROSEN, S
中科院分区：
文献类型：
--
作者：
HEYMAN, SN;BREZIS, M;ROSEN, S
由于人类急性肾功能衰竭（ARF）通常是多次而不是单次损伤的结果，我们使用了联合治疗来诱导大鼠ARF。单肾切除，盐耗尽大鼠注射吲哚美辛后，放射造影剂管理的ARF。24小时后，血浆肌酸酐从103 ± 0.01升到103 ± 0.01。3到211 .+-. 22 μ mol/升（平均值±。SE），肌酐清除率从0.7 ± 0.001下降至0.7 ± 0.001。0.1至0.2 ±。0.04 ml/min（P < 0.001）。严重损伤局限于外髓，包括髓厚升支（mTAL）坏死、肾小管塌陷和管型。除近曲小管外，其他肾单位节段无损伤，近曲小管显示源自侧界膜的空泡形成，类似于人类造影剂肾病中报告的变化。mTAL的细胞损伤包括线粒体肿胀、核固缩、细胞质破裂伴钙化;这些变化在外髓质的最深区域最为严重，远离氧气供应的区域中的直血管。具有严重损伤的mTAL的分数为30 . ±.损伤程度与血肌酐升高相关（r = 0.8，P < 0.001）。因此，mTAL损伤的性质与在无细胞培养基灌注的离体肾脏中观察到的选择性病变相似，并且被证明是由于主动运输mTAL的高需氧量与肾髓质的微薄氧气供应之间的不平衡造成的。在大鼠中联合多次肾损伤产生ARF，其类似于造影剂肾病的临床综合征，并且特征在于由髓质缺氧调节的选择性mTAL损伤。
Since human acute renal failure (ARF) is frequently the result of multiple rather than single insults, we used a combination of treatment to induce ARF in rats. Uninephrectomized, salt-depleted rats injected with indomethacin developed ARF after administration of radiocontrast. After 24 h, the plasma creatinine rose from 103 .+-. 3 to 211 .+-. 22 .mu.mol/liter (mean .+-. SE) and the creatinine clearance dropped from 0.7 .+-. 0.1 to 0.2 .+-. 0.04 ml/min (P < 0.001). Severe injury was confined to the outer medulla and comprised necrosis of medullary thick ascending limbs (mTALs), tubular collapse, and casts. Other nephron segments were free of damage except for the proximal convoluted tubules which showed vacuole formation originating from lateral limiting membranes that resembled changes reported in human contrast nephropathy. Cell damage to mTALs included mitochondrial swelling, nuclear pyknosis, an cytoplasmic disruption with superimposed calcifications; these changes were most severe in the deepest areas of the outer medulla, away from vasa recta in zones remote from oxygen supply. The fraction of mTALs with severe damage was 30 .+-. 7% (range 2-68) and the extent of injury was correlated with a rise in plasma creatinine (r = 0.8, P < 0.001). Thus, the nature of mTAL injury was similar to the selective lesions observed in isolated kidneys perfused with cell-free medium and was shown to derive from an imbalance between high oxygen demand by actively transporting mTALs and the meager oxygen supply to the renal medulla. Combined multiple renal insults in the rat produce ARF that resembles the clinical syndrome of contrast nephropathy and is characterized by selective mTAL injury conditioned by medullary hypoxia.