Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function.
Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function.
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DOI：
10.1152/ajprenal.2001.281.5.f887
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发表时间：
2001-11
期刊：
影响因子：
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通讯作者：
D. Basile;D. Donohoe;Kelly Roethe;J. Osborn
中科院分区：
文献类型：
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作者：
D. Basile;D. Donohoe;Kelly Roethe;J. Osborn
严重肾缺血急性发作可导致急性肾功能衰竭（ARF）。这些发作之后是特征性的恢复和修复反应，其中肾小管形态和肾功能在大约1个月内完全恢复。然而，这种损伤的慢性影响尚未得到很好的研究。雄性大鼠进行60分钟的双侧缺血再灌注，产生特征性损伤。损伤后动物表现出严重的利尿，在损伤后1周达到峰值（体积：>45 ml/d, ARF vs. 18 ml/d, sham; P < 0.05）。尿流量随后下降，但在40周内与假药组相比仍显著升高。尿浓缩能力的长期改变部分归因于产生高渗髓质间质的能力减弱。到第16周，arf后组出现蛋白尿，并在研究期间持续进展。组织学检查显示，在损伤后4周和8周，小管形态基本正常，但在损伤后40周，小管间质纤维化发生。转化生长因子(TGF)- β 1的表达在损伤后40周升高，但在损伤后4周和8周没有升高。微膜分析显示，与假手术动物相比，arf后组在4、8和40周时，外髓质内条纹的小管周围毛细血管密度减少了约30-50%。此外，arf后大鼠对低剂量的ANG II (15 ng x kg（-1) x min(-1)）表现出显著的升压反应。我们假设严重的缺血性损伤会导致肾毛细血管密度的永久性改变，从而导致尿浓缩缺陷和肾纤维化的易发性。
Acute episodes of severe renal ischemia result in acute renal failure (ARF). These episodes are followed by a characteristic recovery and repair response, whereby tubular morphology and renal function appear completely restored within approximately 1 mo. However, the chronic effects of such an injury have not been well studied. Male rats were subjected to 60-min bilateral ischemia followed by reperfusion, yielding a characteristic injury. Postischemic animals manifested severe diuresis, peaking at 1 wk postinjury (volume: >45 ml/day, ARF vs. 18 ml/day, sham; P < 0.05). Urine flow subsequently declined but remained significantly elevated vs. sham animals for a 40-wk period. The prolonged alteration in urinary concentrating ability was attributable, in part, to a diminished capacity to generate a hypertonic medullary interstitium. By week 16, proteinuria developed in the post-ARF group and progressed for the duration of the study. Histological examination revealed essentially normal tubular morphology at 4 and 8 wk postinjury but the development of tubulointerstitial fibrosis at 40 wk. Transforming growth factor (TGF)-beta1 expression was elevated at 40 wk, but not at 4 and 8 wk postinjury. Microfil analysis revealed an approximately 30-50% reduction in peritubular capillary density in the inner stripe of the outer medulla at 4, 8, and 40 wk in post-ARF groups vs. sham animals. In addition, post-ARF rats manifested a significant pressor response to a low dose of ANG II (15 ng x kg(-1) x min(-1)). We hypothesize that severe ischemic injury results in a permanent alteration of renal capillary density, contributing to a urinary concentrating defect and the predisposition toward the development of renal fibrosis.