Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
J Pharmacol Sci. 2010;114(4):354-65. doi: 10.1254/jphs.10r04cr. Epub 2010 Nov 11.
Sepsis remains the leading cause of death in critically ill patients. A major problem contributing to sepsis-related high mortality is the lack of effective medical treatment. Thus, the key goal in critical care medicine is to develop novel therapeutic strategies that will impact favorably on septic patient outcome. While it is generally accepted that sepsis is an inflammatory state resulting from the systemic response to infection, apoptosis is implicated to be an important mechanism of the death of lymphocytes, gastrointestinal and lung epithelial cells, and vascular endothelial cells associated with the development of multiple organ failure in sepsis. The pivotal role of cell apoptosis is now highlighted by multiple studies demonstrating that prevention of cell apoptosis can improve survival in clinically relevant animal models of sepsis. In this review article, we address the scientific rationale for remedying apoptotic cell death in sepsis and propose that therapeutic efforts aimed at blocking cell signaling pathways leading to apoptosis may represent an attractive target for sepsis therapy.
脓毒症仍然是危重病患者死亡的主要原因。导致脓毒症相关高死亡率的一个主要问题是缺乏有效的治疗方法。因此，重症医学的关键目标是开发新的治疗策略，以有利地影响脓毒症患者的预后。虽然人们普遍认为脓毒症是一种炎症状态，是由全身对感染的反应引起的，但细胞凋亡被认为是与多器官衰竭相关的淋巴细胞、胃肠道和肺上皮细胞以及血管内皮细胞死亡的重要机制。多项研究表明，预防细胞凋亡可以提高脓毒症相关动物模型的存活率，这凸显了细胞凋亡的关键作用。在这篇综述文章中，我们探讨了在脓毒症中纠正细胞凋亡的科学依据，并提出针对导致细胞凋亡的细胞信号通路的治疗方法可能是脓毒症治疗的一个有吸引力的靶点。
