Ayala Juan C, Grismaldo Adriana, Aristizabal-Pachon Andres F, Mikhaylenko Elizaveta V, Nikolenko Vladimir N, Mikhaleva Liudmila M, Somasundaram Siva G, Kirkland Cecil E, Aliev Gjumrakch, Morales Ludis
Facultad de Ciencias, Pontificia Universidad Javeriana, Bogota D.C. Carrera 7 No. 40, Colombia.
Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C. Carrera 7 No. 40, Colombia.
Curr Pharm Des. 2021;27(27):3074-3081. doi: 10.2174/1381612826666201207112931.
In patients admitted to the Intensive Care Unit (ICU), mortality is high due to multiple organ damage. Mitochondrial dysfunction and impaired oxygen consumption, as causative mechanisms, play a significant role in reducing the activity of immune cells in sepsis, resulting in the progression of the multiple organ dysfunction syndromes (MODS). The evaluation of mitochondrial function in critical care patients in the immune cells, especially in lymphocytes, could reveal the target point that determines mitochondrial failure.
To find the relationship between mitochondrial reactive oxygen species production (mROS), mitochondrial membrane potential (ΔΨm), and mitochondrial oxygen consumption (mVO) in peripheral plasma lymphocytes collected from ICU patients. We also compared these three characteristic mitochondrial functions with C-reactive protein (CRP), serum lactate, and central venous saturation (SvO) that would enable the prediction of the ultimate outcome.
Isolated lymphocytes from 54 critical care patients with SIRS by sepsis and non-sepsis etiologies were analyzed with flow cytometry by staining with dihydroethidium and JC-1, measuring mROS, ΔΨm, and mVO. Clinical variables, such as serum lactate (mmol/L) and C-reactive protein (mg/L) from peripheral blood, were measured in the first 24 hours of admission. A confounding analysis was performed using logistic regression, and a p-value of <0.05 was considered statistically significant.
It has been confirmed that there is a drastic increase in reactive oxygen species (ROS) and mVO2 in critically ill patients immediately after exposure to the insult pathogen-associated molecular pattern /damageassociated molecular pattern (PAMPS/DAMPS) and continued for the first 24 hours thereafter. The results showed no significant alterations in the mitochondrial membrane potential (ΔΨm) compared with the lymphocytes in controls. A significant correlation between CRP and SvO and a strong positive relationship between CRP, values above 3 mg/l, and white blood cells were observed.
Lymphocytes from patients with SIRS displayed higher mitochondrial respiratory capacities and reactive oxygen species production compared with controls. Clinical markers of inflammation indirectly evaluate the mitochondrial function, most of which have been validated in a clinical setting.
在重症监护病房（ICU）收治的患者中，由于多器官损伤，死亡率很高。线粒体功能障碍和氧消耗受损作为致病机制，在脓毒症中免疫细胞活性降低方面起重要作用，导致多器官功能障碍综合征（MODS）的进展。评估重症监护患者免疫细胞尤其是淋巴细胞中的线粒体功能，可能揭示决定线粒体功能衰竭的靶点。
探讨从ICU患者外周血淋巴细胞中分离出的线粒体活性氧生成（mROS）、线粒体膜电位（ΔΨm）和线粒体氧消耗（mVO）之间的关系。我们还将这三种线粒体功能特征与C反应蛋白（CRP）、血清乳酸和中心静脉血氧饱和度（SvO）进行比较，以预测最终结局。
通过流式细胞术对54例因脓毒症和非脓毒症病因导致全身炎症反应综合征（SIRS）的重症监护患者分离的淋巴细胞进行分析，用二氢乙锭和JC-1染色，测量mROS、ΔΨm和mVO。入院后24小时内测量外周血中的临床变量，如血清乳酸（mmol/L）和C反应蛋白（mg/L）。采用逻辑回归进行混杂分析，p值<0.05被认为具有统计学意义。
已证实，重症患者在接触损伤病原体相关分子模式/损伤相关分子模式（PAMPS/DAMPS）后，活性氧（ROS）和mVO2立即急剧增加，并在随后的24小时内持续增加。结果显示，与对照组淋巴细胞相比，线粒体膜电位（ΔΨm）无显著变化。观察到CRP与SvO之间存在显著相关性，CRP值高于3mg/l与白细胞之间存在强正相关。
与对照组相比，SIRS患者的淋巴细胞表现出更高的线粒体呼吸能力和活性氧生成。炎症的临床标志物间接评估线粒体功能，其中大多数已在临床环境中得到验证。
