Yang Rong-li, Wang Xiao-ting, Liu Da-wei, Liu Si-bo
Critical Care Medicine Department, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Kidney Blood Press Res. 2014;39(4):240-51. doi: 10.1159/000355801. Epub 2014 Aug 6.
BACKGROUND/AIMS: Acute kidney injury (AKI) during septic shock, which is one of the most common clinical syndromes in the intensive care unit (ICU), has a high mortality rate and poor prognosis, partly because of a poor understanding of the pathogenesis of renal dysfunction during septic shock. Although ischemic injury of the kidney has been reported to result from adenosine triphosphate (ATP) depletion, increasing evidence has demonstrated that AKI occurs in the absence of renal hypoperfusion and even occurs during normal or increased renal blood flow (RBF); nevertheless, whether energy metabolism disorder is involved in septic AKI and whether it changes according to renal hemodynamics have not been established. Moreover, tubular cell apoptosis, which is closely related to ATP depletion, rather than necrosis, has been shown to be the major form of cell injury during AKI.
We used canine endotoxin shock models to investigate the hemodynamics, renal energy metabolism, renal oxygen metabolism, and pathological changes during septic AKI and to explore the underlying mechanisms of septic AKI.
The present results revealed that the nicotinamide adenine dinucleotide (NAD+) pool and the ATP/adenosine diphosphate (ADP) ratio were significantly decreased during the early phase of septic AKI, which is accompanied by a decreased renal oxygen extraction ratio (O2ER%) and decreased renal oxygen consumption (VO2). Furthermore, significant apoptosis was observed following renal dysfunction. RBF and renal oxygen delivery were not significantly altered.
These results suggest that imbalanced energy metabolism, rather than tubular cell apoptosis, may be the initiator of renal dysfunction during septic shock.
背景/目的:脓毒性休克期间的急性肾损伤(AKI)是重症监护病房(ICU)中最常见的临床综合征之一,死亡率高且预后差,部分原因是对脓毒性休克期间肾功能障碍的发病机制了解不足。虽然有报道称肾缺血损伤是由三磷酸腺苷(ATP)耗竭引起的,但越来越多的证据表明,AKI在没有肾灌注不足的情况下也会发生,甚至在肾血流量(RBF)正常或增加时也会发生;然而,能量代谢紊乱是否参与脓毒症性AKI以及它是否会根据肾血流动力学发生变化尚未明确。此外,与ATP耗竭密切相关的肾小管细胞凋亡而非坏死已被证明是AKI期间细胞损伤的主要形式。
我们使用犬内毒素休克模型来研究脓毒症性AKI期间的血流动力学、肾能量代谢、肾氧代谢和病理变化,并探讨脓毒症性AKI的潜在机制。
目前的结果显示,在脓毒症性AKI的早期阶段,烟酰胺腺嘌呤二核苷酸(NAD+)池和ATP/二磷酸腺苷(ADP)比值显著降低,同时伴有肾氧摄取率(O2ER%)降低和肾氧耗量(VO2)降低。此外,在肾功能障碍后观察到明显的细胞凋亡。RBF和肾氧输送没有显著改变。
这些结果表明,能量代谢失衡而非肾小管细胞凋亡可能是脓毒性休克期间肾功能障碍的起始因素。