Karlsson Michael, Hara Naomi, Morata Saori, Sjövall Fredrik, Kilbaugh Todd, Hansson Magnus J, Uchino Hiroyoki, Elmér Eskil
*Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden †Department of Anesthesiology, Tokyo Medical University ‡Department of Human Genetics, National Center for Child Health and Development, Tokyo, Japan §Intensive Care Unit, University Hospital of Copenhagen, Copenhagen, Denmark ¶Perelman School of Medicine at the University of Pennsylvania, Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Shock. 2016 Apr;45(4):404-10. doi: 10.1097/SHK.0000000000000525.
Mitochondrial function is thought to play a role in sepsis-induced multiple organ failure. However, the temporal and organ-specific alterations in mitochondrial function have yet to be fully elucidated. Many studies show reduced phosphorylating capacity, while others have indicated that mitochondrial respiration is enhanced. The objective of this study was to evaluate the temporal dynamics of brain and liver mitochondrial function in a mouse model of sepsis.Sepsis was induced by cecal ligation and puncture. Controls were sham operated. Using high-resolution respirometry, brain and liver homogenates from 31 C57BL/6 mice were analyzed at either 6 or 24 h. Reactive oxygen species (ROS) production was simultaneously measured in brain samples using fluorometry.Septic brain tissue exhibited an early increased uncoupling of respiration. Temporal changes between the two time points were diminutive and no difference in ROS production was detected.Liver homogenate from the septic mice displayed a significant increase in the respiratory control ratio at 6 h. In the 24-h group, the rate of maximal oxidative phosphorylation, as well as LEAK respiration, was significantly increased compared with controls and the resultant respiratory control ratio was also significantly increased. Maximal protonophore-induced respiratory (uncoupled) capacity was similar between the two treatment groups.The present study suggests a diverse and tissue-specific mitochondrial respiratory response to sepsis. The brain displayed an early impaired mitochondrial respiratory efficiency. In the liver the primary finding was a substantial activation of the maximal phosphorylating capacity.
线粒体功能被认为在脓毒症诱导的多器官功能衰竭中起作用。然而，线粒体功能的时间和器官特异性改变尚未完全阐明。许多研究表明磷酸化能力降低，而其他研究则表明线粒体呼吸增强。本研究的目的是评估脓毒症小鼠模型中脑和肝线粒体功能的时间动态变化。通过盲肠结扎和穿刺诱导脓毒症。对照组进行假手术。使用高分辨率呼吸测定法，在6小时或24小时时分析31只C57BL/6小鼠的脑和肝匀浆。使用荧光测定法同时测量脑样本中的活性氧（ROS）产生。脓毒症脑组织早期呼吸解偶联增加。两个时间点之间的时间变化很小，未检测到ROS产生的差异。脓毒症小鼠的肝匀浆在6小时时呼吸控制率显著增加。在24小时组中，与对照组相比，最大氧化磷酸化率以及LEAK呼吸显著增加，并且由此产生的呼吸控制率也显著增加。两个治疗组之间最大质子载体诱导的呼吸（解偶联）能力相似。本研究表明脓毒症存在多样的、组织特异性的线粒体呼吸反应。脑显示早期线粒体呼吸效率受损。在肝脏中，主要发现是最大磷酸化能力的大量激活。
