PDF(Pubmed)
Abstract：
Acute kidney ischemia-reperfusion (IR) injury is a life-threatening condition that predisposes individuals to chronic kidney disease. Since the kidney is one of the most energy-demanding organs in the human body and mitochondria are the powerhouse of cells, mitochondrial dysfunction plays a central role in the pathogenesis of IR-induced acute kidney injury. Mitochondrial dysfunction causes a reduction in adenosine triphosphate production, loss of mitochondrial dynamics (represented by persistent fragmentation), and impaired mitophagy. Furthermore, the pathological accumulation of succinate resulting from fumarate reduction under oxygen deprivation (ischemia) in the reverse flux of the Krebs cycle can eventually lead to a burst of reactive oxygen species driven by reverse electron transfer during the reperfusion phase. Accumulating evidence indicates that improving mitochondrial function, biogenesis, and dynamics, and normalizing metabolic reprogramming within the mitochondria have the potential to preserve kidney function during IR injury and prevent progression to chronic kidney disease. In this review, we summarize recent advances in understanding the detrimental role of metabolic reprogramming and mitochondrial dysfunction in IR injury and explore potential therapeutic strategies for treating kidney IR injury.
摘要：
急性肾缺血再灌注(IR)损伤是危及生命的病症,其使个体易患慢性肾病。由于肾脏是人体最需要能量的器官之一，而线粒体是细胞的动力，线粒体功能障碍在IR诱导的急性肾损伤的发病机制中起着重要作用。线粒体功能障碍导致三磷酸腺苷产生减少，线粒体动力学的丧失(由持续的碎片化表示)，和线粒体自噬受损。此外，在Krebs循环的反向通量中，在缺氧（缺血）下由富马酸盐减少引起的琥珀酸盐的病理性积累最终会导致在再灌注阶段由反向电子转移驱动的活性氧爆发。越来越多的证据表明，改善线粒体功能，生物发生，和动态，线粒体内的代谢重编程正常化有可能在IR损伤期间保持肾功能并防止进展为慢性肾病。在这次审查中,我们总结了在了解代谢重编程和线粒体功能障碍在IR损伤中的有害作用方面的最新进展，并探索了治疗肾脏IR损伤的潜在治疗策略。
