Department of Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Nephrol Dial Transplant. 2012 May;27(5):1721-8. doi: 10.1093/ndt/gfs100.
Hypoxia plays a role in ischemic, toxic and sepsis-induced acute kidney injury. Evolving hypoxia triggers renal adaptive responses that may mitigate the insult, leading to sublethal forms of cell injury. The unique capability of the kidney to downregulate oxygen consumption for tubular transport could represent one such adaptive response which promotes maintenance of renal oxygenation, thereby preserving cellular integrity. Tran et al. recently explored a novel mechanism that might prevent tubular damage by downregulation of mitochondrial biogenesis and oxygen consumption. Using expression profiling of kidney RNA in endotoxemic rodents and complementary studies in vitro and in PGC-1α knockout mice, they found a sepsis-related decline in PPARγ coactivator-1α (PGC-1α) expression and of PGC-1α-dependent genes involved in oxidative phosphorylation. This response may explain their observation of a paradoxical preservation of kidney oxygenation and structural integrity in sepsis, despite reduced renal blood flow and oxygen delivery. Thus, resetting of mitochondrial respiration and oxygen consumption during sepsis might be added to the growing list of adaptive responses that occur during hypoxic stress. This review will focus on these mechanisms that mitigate evolving hypoxic injury, even at the expense of transient renal dysfunction.
缺氧在缺血性、毒性和脓毒症引起的急性肾损伤中起作用。不断变化的缺氧会引发肾脏的适应性反应，从而减轻损伤，导致亚致死性细胞损伤。肾脏下调管状运输耗氧量的独特能力可能代表了一种适应性反应，有助于维持肾脏的氧合作用，从而保持细胞的完整性。Tran 等人最近研究了一种通过下调线粒体生物发生和耗氧量来防止管状损伤的新机制。他们通过检测内毒素血症啮齿动物的肾脏 RNA 表达谱，并在体外和 PGC-1α 敲除小鼠中进行补充研究，发现了与脓毒症相关的 PPARγ 共激活因子 1α（PGC-1α）表达和参与氧化磷酸化的 PGC-1α 依赖性基因的下降。这一反应可以解释他们观察到的尽管肾血流量和氧输送减少，但脓毒症时肾脏氧合和结构完整性的反常保留。因此，在脓毒症期间重置线粒体呼吸和耗氧量可能会被添加到缺氧应激期间发生的不断增加的适应性反应列表中。这篇综述将重点介绍这些减轻不断发展的缺氧损伤的机制，即使是以暂时的肾功能障碍为代价。
