Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
AT-enheten, Uppsala University Hospital, Uppsala, Sweden.
Am J Physiol Renal Physiol. 2020 Dec 1;319(6):F1067-F1072. doi: 10.1152/ajprenal.00162.2020. Epub 2020 Oct 12.
Acute kidney injury (AKI) is a significant clinical problem associated with poor outcome. The kidney, due to its inhomogeneous blood flow, is particularly susceptible to changes in oxygen delivery, and intrarenal hypoxia is a hallmark of AKI and progression to chronic kidney disease. However, the role of intrarenal hypoxia per se in the recovery from an ischemic insult is presently unclear. The present study was designed to investigate ) the role of systemic hypoxia in the acute progression and recovery of AKI and ) whether increased intrarenal oxygenation improves recovery from an ischemic insult. Anesthetized male Sprague-Dawley rats were subjected to unilateral warm renal ischemia for 45 min followed by 2 h of reperfusion under systemic hypoxia (10% inspired oxygen), normoxia (21% inspired oxygen), or hyperoxia (60% inspired oxygen). Intrarenal oxygen tension was successfully manipulated by altering the inspired oxygen. Glomerular filtration rate (GFR) before the ischemic insult was independent of intrarenal oxygen tension. GFR during the recovery from the ischemic insult was significantly lower compared with baseline in all groups (3 ± 1%, 13 ± 1%, and 30 ± 11% of baseline for hypoxia, normoxia, and hyperoxia, respectively). However, GFR was significantly higher in hyperoxia than hypoxia ( < 0.05, hypoxia vs. hyperoxia). During recovery, renal blood flow was only reduced in hyperoxia, as a consequence of increased renal vascular resistance. In conclusion, the present study demonstrates that renal function during the recovery from an ischemic insult is dependent on intrarenal oxygen availability, and normobaric hyperoxia treatment has the potential to protect kidney function.
急性肾损伤 (AKI) 是与不良预后相关的重要临床问题。肾脏由于血流分布不均匀，特别容易受到氧输送变化的影响，而肾内缺氧是 AKI 和进展为慢性肾脏病的标志。然而，目前尚不清楚肾内缺氧本身在缺血性损伤恢复中的作用。本研究旨在探讨全身性缺氧在 AKI 的急性进展和恢复中的作用，以及增加肾内氧合是否能改善缺血性损伤的恢复。麻醉雄性 Sprague-Dawley 大鼠接受单侧温热肾缺血 45 分钟，然后在全身缺氧（10%吸入氧）、常氧（21%吸入氧）或高氧（60%吸入氧）下再灌注 2 小时。通过改变吸入氧来成功地调节肾内氧张力。缺血前的肾小球滤过率（GFR）与肾内氧张力无关。与基线相比，所有组在缺血后恢复期间的 GFR 均显著降低（分别为 3±1%、13±1%和 30±11%）。然而，高氧组的 GFR 明显高于低氧组（<0.05，低氧组与高氧组相比）。在恢复期间，仅在高氧组中观察到肾血流减少，这是由于肾血管阻力增加所致。总之，本研究表明，缺血后恢复期间的肾功能取决于肾内氧供应，常压低氧治疗有可能保护肾功能。
