Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia.
Institute of Chemistry, Technology and Metallurgy, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
Int J Mol Sci. 2024 Jul 16;25(14):7770. doi: 10.3390/ijms25147770.
Sepsis-induced multiple organ dysfunction arises from the highly complex pathophysiology encompassing the interplay of inflammation, oxidative stress, endothelial dysfunction, mitochondrial damage, cellular energy failure, and dysbiosis. Over the past decades, numerous studies have been dedicated to elucidating the underlying molecular mechanisms of sepsis in order to develop effective treatments. Current research underscores liver and cardiac dysfunction, along with acute lung and kidney injuries, as predominant causes of mortality in sepsis patients. This understanding of sepsis-induced organ failure unveils potential therapeutic targets for sepsis treatment. Various novel therapeutics, including melatonin, metformin, palmitoylethanolamide (PEA), certain herbal extracts, and gut microbiota modulators, have demonstrated efficacy in different sepsis models. In recent years, the research focus has shifted from anti-inflammatory and antioxidative agents to exploring the modulation of energy metabolism and gut microbiota in sepsis. These approaches have shown a significant impact in preventing multiple organ damage and mortality in various animal sepsis models but require further clinical investigation. The accumulation of this knowledge enriches our understanding of sepsis and is anticipated to facilitate the development of effective therapeutic strategies in the future.
脓毒症诱导的多器官功能障碍源于高度复杂的病理生理学,包括炎症、氧化应激、内皮功能障碍、线粒体损伤、细胞能量衰竭和菌群失调的相互作用。在过去的几十年中,许多研究致力于阐明脓毒症的潜在分子机制,以开发有效的治疗方法。目前的研究强调肝和心脏功能障碍,以及急性肺和肾损伤,是脓毒症患者死亡的主要原因。对脓毒症诱导的器官衰竭的这种理解揭示了脓毒症治疗的潜在治疗靶点。各种新型治疗方法,包括褪黑素、二甲双胍、棕榈酸乙醇酰胺(PEA)、某些草药提取物和肠道微生物群调节剂,已在不同的脓毒症模型中显示出疗效。近年来,研究重点已从抗炎和抗氧化剂转向探索脓毒症中能量代谢和肠道微生物群的调节。这些方法在预防各种动物脓毒症模型中的多器官损伤和死亡率方面显示出显著效果,但需要进一步的临床研究。这些知识的积累丰富了我们对脓毒症的理解,并有望促进未来有效治疗策略的发展。