Mitochondrial Research Laboratory, IDIBAPS, University of Barcelona, Internal Medicine Department, Hospital Clínic of Barcelona (HCB, Barcelona) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Valencia).
J Infect Dis. 2012 Feb 1;205(3):392-400. doi: 10.1093/infdis/jir764. Epub 2011 Dec 16.
Sepsis is associated with mitochondrial dysfunction and impaired oxygen consumption, which may condition clinical outcome independent of tissue oxygenation. However, mitochondrial role in sepsis severity remains unknown. We aimed to characterize mitochondrial function in sepsis, establish its origin and cellular consequences, and determine its correlation with clinical symptoms and outcome.
Different markers of mitochondrial activity, nitrosative and oxidative stress, apoptosis, and inflammation were measured in peripheral blood mononuclear cells (PBMCs) and plasma of 19 septic patients and 20 controls. Plasma capacity to induce mitochondrial dysfunction was assessed in muscle mitochondria from 5 healthy individuals incubated with plasma of septic patients or controls.
Despite unaltered mitochondrial mass and protein synthesis, enzymatic mitochondrial complexes I, III, and IV and oxygen consumption were significantly inhibited in sepsis. Septic plasma tended to reduce oxygen consumption of healthy mitochondria and showed significantly increased amounts of extracellular mitochondrial DNA and inflammatory cytokines, especially in patients presenting adverse outcome. Active nuclear factor kappa-light-chain enhancer of activated B cells (NFKB) was also significantly increased, together with nitric oxide, oxidative stress and apoptosis. Additionally, sepsis severity significantly correlated with complex I inhibition, NFKB activation and intercellular adhesion molecule expression.
A plasmatic factor such as nitric oxide, increased in inflammation and able to induce mitochondrial dysfunction, oxidative stress and apoptosis, may be responsible for cell damage in sepsis. Together with bacterial infection, leakage of mitochondrial DNA from damaged cells into circulation could contribute to systemic inflammatory response syndrome. Mitochondrial dysfunction and inflammation correlate with sepsis severity and outcome, becoming targets for supporting therapies.
脓毒症与线粒体功能障碍和耗氧量减少有关，这可能会导致临床结局发生变化，而与组织氧合无关。然而，线粒体在脓毒症严重程度中的作用尚不清楚。我们旨在描述脓毒症中的线粒体功能，确定其起源和细胞后果，并确定其与临床症状和结局的相关性。
在 19 例脓毒症患者和 20 例对照者的外周血单核细胞（PBMC）和血浆中测量了不同的线粒体活性、硝化和氧化应激、凋亡和炎症标志物。用来自 5 名健康个体的肌肉线粒体评估了脓毒症患者或对照者的血浆在诱导线粒体功能障碍方面的能力。
尽管线粒体质量和蛋白质合成没有改变，但酶促线粒体复合物 I、III 和 IV 以及耗氧量在脓毒症中显著受到抑制。脓毒症患者的血浆往往会降低健康线粒体的耗氧量，并且显示出明显增加的细胞外线粒体 DNA 和炎症细胞因子，尤其是在出现不良结局的患者中。活性核因子 kappa 轻链增强子的 B 细胞（NFKB）也显著增加，同时还有一氧化氮、氧化应激和凋亡。此外，脓毒症严重程度与复合物 I 抑制、NFKB 激活和细胞间黏附分子表达显著相关。
一种如一氧化氮的血浆因子，在炎症中增加，能够诱导线粒体功能障碍、氧化应激和凋亡，可能是脓毒症中细胞损伤的原因。与细菌感染一起，受损细胞中线粒体 DNA 的泄漏进入循环可能导致全身炎症反应综合征。线粒体功能障碍和炎症与脓毒症的严重程度和结局相关，成为支持治疗的靶点。
