Dare Anna J, Bolton Eleanor A, Pettigrew Gavin J, Bradley J Andrew, Saeb-Parsy Kourosh, Murphy Michael P
Medical Research Council Mitochondrial Biology Unit, Cambridge BioMedical Campus, Hills Road, Cambridge CB2 0XY, UK.
Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
Redox Biol. 2015 Aug;5:163-168. doi: 10.1016/j.redox.2015.04.008. Epub 2015 Apr 29.
Ischemia-reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury.
肾脏缺血再灌注（IR）损伤发生在一系列具有临床重要意义的情况下，包括低血压、脓毒症以及诸如心脏搭桥手术和肾脏移植等外科手术中，会导致急性肾损伤（AKI）。线粒体氧化损伤是IR损伤早期的一个重要因素，可能引发有害的炎症反应。在此，我们评估了线粒体靶向抗氧化剂MitoQ是否能减少IR损伤期间的氧化损伤，从而保护肾功能。为此，我们通过双侧阻断肾血管使小鼠肾脏遭受体内缺血，随后再灌注长达24小时。这导致了肾功能障碍，通过肌酐清除率降低来衡量，同时氧化损伤标志物增加。在缺血前15分钟给小鼠静脉注射MitoQ可保护肾脏免受损伤和功能障碍。这些数据表明，线粒体氧化损伤导致肾脏IR损伤，并且线粒体靶向抗氧化剂如MitoQ是治疗IR损伤所致肾功能障碍的潜在疗法。
