Department of Radiology, Medical School, University of Patras, Rio-Patras, Greece.
Am J Nephrol. 2012;36(3):278-86. doi: 10.1159/000341871. Epub 2012 Sep 7.
BACKGROUND/AIMS: Parstatin is a 41-mer peptide formed by proteolytic cleavage on activation of the protease-activated receptor 1. Parstatin was recently found to be cardioprotective against myocardial ischemia/reperfusion (IR) injury. In the present study, it was hypothesized that parstatin would protect the kidneys in acute renal failure.
We investigated the effects of parstatin on the renal dysfunction and injury caused either by renal IR injury or contrast-induced nephropathy (CIN) in two animal models. Renal IR injury was induced in rats by bilateral occlusion of renal arteries and veins for 45 min followed by 4 h of reperfusion, while CIN was induced in rabbits by intravenous injection of the radiocontrast medium Iopromide.
Treatment with parstatin 15 min before or immediately after renal ischemia attenuated the resulting renal dysfunction as demonstrated by the improved biochemical indicators (serum creatinine and fractional excretion of Na(+)) and scintigraphic analysis. The effect was dose depended and provided evidence for a more prominent protection of tubular than glomerulal function. Histopathological examination of the kidneys revealed severe renal damage, which was significantly suppressed by the parstatin. Similarly, administration of a single dose of parstatin before the induction of CIN significantly protected against the resulting renal dysfunction and histologically evidenced renal tubular injury.
These results suggest that parstatin is able to act as nephroprotective agent and may be useful in enhancing the tolerance of the kidney against renal injury associated with clinical conditions of acute renal failure. Further investigation on the mechanism underlying the nephroprotective properties of parstatin is deemed necessary.
背景/目的：Parstatin 是一种 41 肽，在激活蛋白酶激活受体 1 时通过蛋白水解切割形成。最近发现 Parstatin 对心肌缺血/再灌注（IR）损伤具有心脏保护作用。在本研究中，假设 Parstatin 可保护急性肾衰竭中的肾脏。
我们研究了 Parstatin 对两种动物模型中由肾 IR 损伤或对比剂诱导的肾病（CIN）引起的肾功能障碍和损伤的影响。通过双侧肾动静脉闭塞 45 分钟然后再灌注 4 小时，在大鼠中诱导肾 IR 损伤，而在兔中通过静脉注射放射性对比剂碘普罗胺诱导 CIN。
在肾缺血前 15 分钟或立即给予 Parstatin 治疗可改善生化指标（血清肌酐和 Na(+)的分数排泄）和闪烁照相分析，从而减轻由此引起的肾功能障碍。该作用呈剂量依赖性，并为肾小管功能比肾小球功能提供了更明显的保护证据。肾脏的组织病理学检查显示严重的肾损伤，Parstatin 显著抑制了这种损伤。同样，在 CIN 诱导前单次给予 Parstatin 可显著防止由此引起的肾功能障碍和组织学证据表明的肾小管损伤。
这些结果表明，Parstatin 能够作为肾脏保护剂，可能有助于增强肾脏对与急性肾衰竭相关的临床情况引起的肾损伤的耐受性。需要进一步研究 Parstatin 的肾脏保护特性的机制。
