Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Free Radic Biol Med. 2011 Sep 1;51(5):1062-7. doi: 10.1016/j.freeradbiomed.2010.10.704. Epub 2010 Oct 27.
Rhabdomyolysis-induced renal failure represents up to 15% of all cases of acute renal failure. Many studies over the past 4 decades have demonstrated that accumulation of myoglobin in the kidney is central in the mechanism leading to kidney injury. However, some discussion exists regarding the mechanism mediating this oxidant injury. Although the free-iron-catalyzed Fenton reaction has been proposed to explain the tissue injury, more recent evidence strongly suggests that the main cause of oxidant injury is myoglobin redox cycling and generation of oxidized lipids. These molecules can propagate tissue injury and cause renal vasoconstriction, two of the three main conditions associated with acute renal failure. This review presents the evidence supporting the two mechanisms of oxidative injury, describes the central role of myoglobin redox cycling in the pathology of renal failure associated with rhabdomyolysis, and discusses the value of therapeutic interventions aiming at inhibiting myoglobin redox cycling for the treatment of rhabdomyolysis-induced renal failure.
横纹肌溶解症导致的肾衰竭占所有急性肾衰竭病例的 15%左右。在过去的 40 年中，许多研究表明，肌红蛋白在肾脏中的积累是导致肾脏损伤的主要机制。然而，对于介导这种氧化损伤的机制仍存在一些争议。虽然已经提出了自由铁催化的芬顿反应来解释组织损伤，但最近的证据强烈表明，氧化损伤的主要原因是肌红蛋白的氧化还原循环和氧化脂质的产生。这些分子可以引发组织损伤并导致肾血管收缩，这是急性肾衰竭的三个主要条件中的两个。本文综述了支持氧化损伤两种机制的证据，描述了肌红蛋白氧化还原循环在横纹肌溶解症相关肾衰竭病理中的核心作用，并讨论了针对抑制肌红蛋白氧化还原循环的治疗干预措施在治疗横纹肌溶解症引起的肾衰竭方面的价值。
