Unidad de Fisiología Molecular, Departamento de Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Nephrol Dial Transplant. 2012 Aug;27(8):3160-9. doi: 10.1093/ndt/gfs014. Epub 2012 Apr 19.
Prophylactic mineralocorticoid receptor (MR) antagonism with spironolactone (Sp) in rats completely prevents renal damage induced by ischemia. Because acute renal ischemia cannot typically be predicted, this study was designed to investigate whether Sp could prevent renal injury after an ischemic/reperfusion insult.
Six groups of male Wistar rats were studied: rats that received a sham abdominal operation (S); rats that underwent 20 min of ischemia and reperfusion for 24 h (I/R) and four groups of rats treated with Sp (20 mg/kg) 0, 3, 6 or 9 h after ischemia.
As expected, I/R resulted in renal dysfunction characterized by a fall in renal blood flow and glomerular filtration rate and severe tubular injury which was confirmed by a significant increase in tubular damage biomarkers including kidney injury molecule-1, heat shock protein 72 and urinary protein excretion. The renal injury induced by I/R was in part due to Rho-kinase, endothelin and angiotensin II type 1 receptor upregulation. Interestingly, Sp administration at 0 and 3 h after ischemia completely reversed and prevented the damage induced by I/R. The protection induced by Sp given 6 h after ischemia was partial, but no protection was observed by administering Sp 9 h after ischemia.
Our results show that MR antagonism administered, either immediately or 3 h after I/R, effectively prevented ischemic acute renal injury, indicating that spironolactone is a promising agent for preventing acute kidney injury once an ischemic insult has occurred.
螺内酯（Sp）预防性抑制矿皮质激素受体（MR）可完全预防大鼠缺血引起的肾损伤。由于急性肾缺血通常无法预测，因此本研究旨在探讨 Sp 是否可预防缺血再灌注损伤后的肾损伤。
研究了 6 组雄性 Wistar 大鼠：接受假腹部手术的大鼠（S）；经历 20 分钟缺血和 24 小时再灌注的大鼠（I/R），以及四组在缺血后 0、3、6 或 9 小时接受 Sp（20mg/kg）治疗的大鼠。
正如预期的那样，I/R 导致肾功能障碍，表现为肾血流量和肾小球滤过率下降，以及严重的肾小管损伤，这通过肾小管损伤生物标志物（包括肾损伤分子-1、热休克蛋白 72 和尿蛋白排泄）的显著增加得到证实。I/R 引起的肾损伤部分归因于 Rho-kinase、内皮素和血管紧张素 II 型 1 受体的上调。有趣的是，缺血后 0 和 3 小时给予 Sp 可完全逆转和预防 I/R 引起的损伤。缺血后 6 小时给予 Sp 引起的保护是部分的，但缺血后 9 小时给予 Sp 则没有保护作用。
我们的结果表明，MR 拮抗剂在 I/R 后立即或 3 小时给予，可有效预防缺血性急性肾损伤，表明螺内酯是在发生缺血性损伤后预防急性肾损伤的一种有前途的药物。
