Cinel Ismail, Opal Steven M
Division of Critical Care Medicine, The Robert Wood Johnson School of Medicine, The University of Medicine and Dentistry of New Jersey, Camden, NJ, USA.
Crit Care Med. 2009 Jan;37(1):291-304. doi: 10.1097/CCM.0b013e31819267fb.
Remarkable progress has been made during the last decade in defining the molecular mechanisms that underlie septic shock. This rapidly expanding field is leading to new therapeutic opportunities in the management of severe sepsis.
To provide the clinician with a timely summary of the molecular biology of sepsis and to better understand recent advances in sepsis research.
Medline search of relevant publications in basic mechanisms of sepsis/severe sepsis/septic shock, and selected literature review of other manuscripts about the signalosome, inflammasome, apoptosis, or mechanisms of shock. DATA SYNTHESIS AND FINDINGS: The identification of the toll-like receptors and the associated concept of innate immunity based upon pathogen- or damage-associated molecular pattern molecules allowed significant advances in our understanding of the pathophysiology of sepsis. The essential elements of the inflammasome and signal transduction networks responsible for activation of the host response have now been characterized. Apoptosis, mitochondrial dysfunction, sepsis-related immunosuppression, late mediators of systemic inflammation, control mechanisms for coagulation, and reprogramming of immune response genes all have critical roles in the development of sepsis.
Many of these basic discoveries have direct implications for the clinical management of sepsis. The translation of these "bench-to-bedside" findings into new therapeutic strategies is already underway. This brief review provides the clinician with a primer into the basic mechanisms responsible for the molecular biology of sepsis, severe sepsis, and septic shock.
在过去十年中，在确定脓毒症休克潜在的分子机制方面取得了显著进展。这个迅速发展的领域为严重脓毒症的治疗带来了新的机遇。
为临床医生及时总结脓毒症的分子生物学，并更好地理解脓毒症研究的最新进展。
通过医学文献数据库检索脓毒症/严重脓毒症/脓毒症休克基本机制的相关出版物，并对其他有关信号体、炎性小体、细胞凋亡或休克机制的手稿进行文献综述。资料综合与结果：Toll样受体的鉴定以及基于病原体或损伤相关分子模式分子的固有免疫相关概念，使我们对脓毒症病理生理学的理解取得了重大进展。现在已经明确了负责激活宿主反应的炎性小体和信号转导网络的基本要素。细胞凋亡、线粒体功能障碍、脓毒症相关免疫抑制、全身炎症的晚期介质、凝血控制机制以及免疫反应基因的重新编程在脓毒症的发展中都起着关键作用。
许多这些基础发现对脓毒症的临床管理有直接影响。将这些“从 bench 到 bedside”的发现转化为新的治疗策略的工作已经在进行中。这篇简短的综述为临床医生提供了脓毒症、严重脓毒症和脓毒症休克分子生物学基本机制的入门知识。
