Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida.
Tampa General Hospital, Tampa, Florida.
Am J Physiol Renal Physiol. 2019 Sep 1;317(3):F616-F622. doi: 10.1152/ajprenal.00533.2018. Epub 2019 Jul 10.
Transplanted kidneys usually experience several episodes of ischemia, including cold ischemia during allograft storage in preservation solution. However, previous studies focusing on cold renal ischemia were only carried out in vitro or ex vivo. In the present study, we developed and characterized an in vivo mouse model of renal ischemia-reperfusion injury (IRI) induced exclusively by cold ischemia. C57BL/6 mice underwent right kidney nephrectomy, and the left kidney was kept cool with circulating cold saline in a kidney cup, while body temperature was maintained at 37°C. We clamped the renal pedicle and flushed out the blood inside the kidney with cold saline via an opening on the renal vein. The severity of renal IRI was examined with different ischemic durations. We found that the mice with <2 h of cold ischemia exhibited no significant changes in renal function or histopathology; animals with 3 or 4 h of cold ischemia developed into mild to moderate acute kidney injury with characteristic features, including the elevation in plasma creatinine concentration and reduction in glomerular filtration rate and tubular necrosis, followed by a subsequent recovery. However, mice with 5 h of cold ischemia died in a few days with severe acute kidney injury. In summary, we generated a mouse model of renal IRI induced exclusively by cold ischemia, which mimics graft cold storage in preservation solution, and renal function can be evaluated in vivo.
移植肾脏通常会经历多次缺血事件，包括在保存液中进行同种异体肾保存时的冷缺血。然而，以前专注于冷肾缺血的研究仅在体外或离体进行。在本研究中，我们开发并表征了一种仅由冷缺血引起的体内小鼠肾缺血再灌注损伤 (IRI) 模型。C57BL/6 小鼠接受右肾切除术，左肾在肾杯内用循环冷盐水冷却，同时保持体温在 37°C。我们夹闭肾蒂，通过肾静脉上的开口用冷盐水冲洗肾内的血液。用不同的缺血持续时间来检查肾 IRI 的严重程度。我们发现，冷缺血 <2 小时的小鼠肾功能或组织病理学没有明显变化；冷缺血 3 或 4 小时的动物发展为轻度至中度急性肾损伤，具有特征性表现，包括血浆肌酐浓度升高、肾小球滤过率和肾小管坏死减少，随后恢复。然而，冷缺血 5 小时的小鼠在几天内死于严重的急性肾损伤。总之，我们生成了一种仅由冷缺血引起的小鼠肾 IRI 模型，该模型模拟了保存液中的供体冷储存，并且可以在体内评估肾功能。
