关键词: Inflammation Mitochondria Mitochondrial dysfunction Oxidative phosphorylation Respirometry Sepsis

来  源:   DOI:10.5492/wjccm.v12.i3.139   PDF(Pubmed)

Abstract:
Sepsis represents a deranged and exaggerated systemic inflammatory response to infection and is associated with vascular and metabolic abnormalities that trigger systemic organic dysfunction. Mitochondrial function has been shown to be severely impaired during the early phase of critical illness, with a reduction in biogenesis, increased generation of reactive oxygen species and a decrease in adenosine triphosphate synthesis of up to 50%. Mitochondrial dysfunction can be assessed using mitochondrial DNA concentration and respirometry assays, particularly in peripheral mononuclear cells. Isolation of monocytes and lymphocytes seems to be the most promising strategy for measuring mitochondrial activity in clinical settings because of the ease of collection, sample processing, and clinical relevance of the association between metabolic alterations and deficient immune responses in mononuclear cells. Studies have reported alterations in these variables in patients with sepsis compared with healthy controls and non-septic patients. However, few studies have explored the association between mitochondrial dysfunction in immune mononuclear cells and unfavorable clinical outcomes. An improvement in mitochondrial parameters in sepsis could theoretically serve as a biomarker of clinical recovery and response to oxygen and vasopressor therapies as well as reveal unexplored pathophysiological mechanistic targets. These features highlight the need for further studies on mitochondrial metabolism in immune cells as a feasible tool to evaluate patients in intensive care settings. The evaluation of mitochondrial metabolism is a promising tool for the evaluation and management of critically ill patients, especially those with sepsis. In this article, we explore the pathophysiological aspects, main methods of measurement, and the main studies in this field.
摘要:
脓毒症代表对感染的紊乱和过度的全身性炎症反应,并与引发全身性器质性功能障碍的血管和代谢异常有关。线粒体功能已被证明在危重疾病的早期阶段严重受损,随着生物发生的减少,增加活性氧的产生和三磷酸腺苷合成的减少高达50%。线粒体功能障碍可以使用线粒体DNA浓度和呼吸测定来评估,特别是在外周单核细胞中。由于易于收集,单核细胞和淋巴细胞的分离似乎是在临床环境中测量线粒体活性的最有前途的策略。样品处理,以及单个核细胞中代谢改变与免疫反应缺陷之间关联的临床相关性。研究报告了败血症患者与健康对照和非败血症患者相比,这些变量的变化。然而,很少有研究探讨免疫单核细胞线粒体功能障碍与不良临床结局之间的关系.脓毒症中线粒体参数的改善理论上可以作为临床恢复和对氧气和血管加压药疗法的反应的生物标志物,并揭示未探索的病理生理机制靶标。这些特征突出表明,需要进一步研究免疫细胞中的线粒体代谢,作为评估重症监护患者的可行工具。线粒体代谢的评估是评估和管理危重病人的一个有前途的工具,尤其是那些有败血症的人.在这篇文章中,我们探索病理生理方面,主要测量方法,以及该领域的主要研究。
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