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.
Int J Mol Sci. 2024 Mar 2;25(5):2912. doi: 10.3390/ijms25052912.
This study aims to analyze post-mortem human cardiac specimens, to verify and evaluate the existence or extent of oxidative stress in subjects whose cause of death has been traced to sepsis, through immunohistological oxidative/nitrosative stress markers. Indeed, in the present study, i-NOS, NOX2, and nitrotyrosine markers were higher expressed in the septic death group when compared to the control group, associated with also a significant increase in 8-OHdG, highlighting the pivotal role of oxidative stress in septic etiopathogenesis. In particular, 70% of cardiomyocyte nuclei from septic death specimens showed positivity for 8-OHdG. Furthermore, intense and massive NOX2-positive myocyte immunoreaction was noticed in the septic group, as nitrotyrosine immunostaining intense reaction was found in the cardiac cells. These results demonstrated a correlation between oxidative and nitrosative stress imbalance and the pathophysiology of cardiac dysfunction documented in cases of sepsis. Therefore, subsequent studies will focus on the expression of oxidative stress markers in other organs and tissues, as well as on the involvement of the intracellular pattern of apoptosis, to better clarify the complex pathogenesis of multi-organ failure, leading to support the rationale for including therapies targeting redox abnormalities in the management of septic patients.
本研究旨在通过免疫组织化学氧化/硝化应激标志物分析死后人心肌标本，以验证和评估死因归因于败血症的患者中氧化应激的存在或程度。事实上，在本研究中，与对照组相比，脓毒症死亡组的 iNOS、NOX2 和硝基酪氨酸标志物表达更高，同时 8-OHdG 显著增加，突出了氧化应激在脓毒症发病机制中的关键作用。特别是，70%的脓毒症死亡标本的心肌细胞核显示 8-OHdG 阳性。此外，在脓毒症组中观察到强烈和大量的 NOX2 阳性肌细胞免疫反应，如在心脏细胞中发现硝基酪氨酸免疫染色强烈反应。这些结果表明氧化和硝化应激失衡与败血症患者心脏功能障碍的病理生理学之间存在相关性。因此，后续研究将集中在其他器官和组织中氧化应激标志物的表达以及细胞内细胞凋亡模式的参与，以更好地阐明多器官衰竭的复杂发病机制，从而支持在脓毒症患者的治疗中纳入针对氧化还原异常的治疗方法的合理性。
