Kohoutová M, Dejmek J, Tůma Z, Kuncová J
Institute of Physiology, Faculty of Medicine in Plzeň, Charles University, Plzeň, Czech Republic.
Physiol Res. 2018 Dec 31;67(Suppl 4):S577-S592. doi: 10.33549/physiolres.934050.
Ample experimental evidence suggests that sepsis could interfere with any mitochondrial function; however, the true role of mitochondrial dysfunction in the pathogenesis of sepsis-induced multiple organ dysfunction is still a matter of controversy. This review is primarily focused on mitochondrial oxygen consumption in various animal models of sepsis in relation to human disease and potential sources of variability in experimental results documenting decrease, increase or no change in mitochondrial respiration in various organs and species. To date, at least three possible explanations of sepsis-associated dysfunction of the mitochondrial respiratory system and consequently impaired energy production have been suggested: 1. Mitochondrial dysfunction is secondary to tissue hypoxia. 2. Mitochondria are challenged by various toxins or mediators of inflammation that impair oxygen utilization (cytopathic hypoxia). 3. Compromised mitochondrial respiration could be an active measure of survival strategy resembling stunning or hibernation. To reveal the true role of mitochondria in sepsis, sources of variability of experimental results based on animal species, models of sepsis, organs studied, or analytical approaches should be identified and minimized by the use of appropriate experimental models resembling human sepsis, wider use of larger animal species in preclinical studies, more detailed mapping of interspecies differences and organ-specific features of oxygen utilization in addition to use of complex and standardized protocols evaluating mitochondrial respiration.
大量实验证据表明，脓毒症可能会干扰任何线粒体功能；然而，线粒体功能障碍在脓毒症诱导的多器官功能障碍发病机制中的真正作用仍存在争议。本综述主要关注脓毒症各种动物模型中线粒体的氧消耗，及其与人类疾病的关系，以及记录不同器官和物种中线粒体呼吸减少、增加或无变化的实验结果的潜在变异来源。迄今为止，至少有三种关于脓毒症相关线粒体呼吸系统功能障碍以及由此导致的能量产生受损的可能解释：1. 线粒体功能障碍继发于组织缺氧。2. 线粒体受到各种毒素或炎症介质的挑战，这些毒素或介质会损害氧利用（细胞病性缺氧）。3. 线粒体呼吸受损可能是一种类似于昏厥或冬眠的生存策略的主动措施。为了揭示线粒体在脓毒症中的真正作用，应通过使用类似于人类脓毒症的适当实验模型、在临床前研究中更广泛地使用大型动物物种、更详细地描绘种间差异以及氧利用的器官特异性特征，此外还应使用评估线粒体呼吸的复杂标准化方案，来识别并最小化基于动物物种、脓毒症模型、研究器官或分析方法的实验结果变异来源。
