Bertozzi Giuseppe, Ferrara Michela, Calvano Mariagrazia, Pascale Natascha, Di Fazio Aldo
SIC Medicina Legale, Via Potito Petrone, 85100 Potenza, Italy.
Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00185 Rome, Italy.
Medicina (Kaunas). 2024 Nov 26;60(12):1949. doi: 10.3390/medicina60121949.
: A large amount of recent evidence suggests that cellular inability to consume oxygen could play a notable part in promoting sepsis as a consequence of mitochondrial dysfunction and oxidative stress. The latter could, in fact, represent a fundamental stage in the evolution of the "natural history" of sepsis. Following a study previously conducted by the same working group on heart samples, the present research project aims to evaluate, through an immunohistochemical study, the existence and/or extent of oxidative stress in the brains of subjects who died due to sepsis and define, after reviewing the literature, its contribution to the septic process to support the use of medications aimed at correcting redox anomalies in the management of septic patients. : 10 cases of subjects who died in healthcare facilities with ante-mortem clinical-laboratory signs that allowed the diagnosis of septic shock were selected as case studies, and 1 case of a subject who died immediately following a road traffic accident was used as a negative control. Samples of the cerebral cortex were then taken, fixed in formalin, and subjected to sections on which an immunohistochemical study was performed using anti-NOX-2, NT, iNOS, and 8-OHdG antibodies. : The results emerging from the present study demonstrate that despite a variable expressivity for the NT, iNOS, and NOX2 markers, the brain samples demonstrated univocal and high positivity for the 8-OHdG marker. : This would allow us to hypothesize how, regardless of the mechanism of production of ROS and NOS (iNOS or NOX2 mediated) and the pathophysiological mechanisms that are triggered during sepsis, oxidative damage to DNA represents the event to which this whole process leads and, in fact, in the literature, is directly correlated to sepsis-dependent mortality. Neurons, conversely, appear to be more sensitive to oxidative stress because of a low number of protective or scavenger molecules (catalase, glutathione peroxidase, GSH, or vitamin E). Therefore, despite reduced production, the manifestation of the damage remains high. This evidence, together with that of the previous study, can only support the introduction of substances with an antioxidant function in the guidelines for the treatment of sepsis.
大量最新证据表明，细胞无法消耗氧气可能在线粒体功能障碍和氧化应激导致脓毒症的过程中起显著作用。事实上，后者可能是脓毒症“自然史”演变的一个基本阶段。在同一工作组之前对心脏样本进行研究之后，本研究项目旨在通过免疫组织化学研究，评估因脓毒症死亡患者大脑中氧化应激的存在情况和/或程度，并在查阅文献后确定其对脓毒症进程的影响，以支持在脓毒症患者管理中使用旨在纠正氧化还原异常的药物。选择10例在医疗机构死亡且生前有临床实验室体征可诊断为感染性休克的患者作为病例研究，1例在道路交通事故后立即死亡的患者作为阴性对照。然后采集大脑皮质样本，用福尔马林固定，并进行切片，使用抗NOX - 2、NT、诱导型一氧化氮合酶（iNOS）和8 - 羟基脱氧鸟苷（8 - OHdG）抗体进行免疫组织化学研究。本研究得出的结果表明，尽管NT、iNOS和NOX2标志物的表达存在差异，但大脑样本对8 - OHdG标志物呈现出明确且高度的阳性反应。这使我们能够推测，无论活性氧（ROS）和一氧化氮合酶（iNOS或NOX2介导）的产生机制以及脓毒症期间触发的病理生理机制如何，DNA的氧化损伤都是整个过程导致的结果，事实上，在文献中，它与脓毒症相关死亡率直接相关。相反，由于保护性或清除性分子（过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽或维生素E）数量较少，神经元似乎对氧化应激更敏感。因此，尽管产生减少，但损伤表现仍然很高。这一证据以及先前研究的证据只能支持在脓毒症治疗指南中引入具有抗氧化功能的物质。
