Jarrar D, Chaudry I H, Wang P
Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence, RI 02903, USA.
Int J Mol Med. 1999 Dec;4(6):575-83. doi: 10.3892/ijmm.4.6.575.
Despite significant advances in the management of trauma victims, sepsis and the ensuing multiple organ failure remain the leading causes of death in the surgical intensive care unit. Although much effort has been focused on the mediators released in large quantities following shock and sepsis, blockade of mediators such as proinflammatory cytokines has not yet resulted in a successful therapy. However, as more studies are forthcoming, the mechanisms responsible for cell and organ dysfunctions following trauma-hemorrhage and sepsis are becoming better understood, and promising new therapeutic approaches are currently being evaluated. In order to understand the precise mechanisms responsible for cellular dysfunction and consequently irreversible organ damage and multiple organ failure, it is important to correlate various pathophysiological changes with mediators and signal transduction pathways at the cellular and subcellular level. In this review we focus first on factors and mediators responsible for producing cell and organ dysfunctions, especially hepatocellular dysfunction, following trauma, hemorrhagic shock, and sepsis. The changes in signaling transduction pathways will also be discussed, specifically the role of mitogen-activated protein kinases, transcription factors, nitric oxide, heat shock proteins, and inflammatory cytokines in the development of cell and organ dysfunctions following trauma-hemorrhage and sepsis. Moreover, potential therapeutic approaches for improving cell and organ functions under adverse circulatory conditions are included.
尽管在创伤患者的治疗方面取得了重大进展，但脓毒症及随之而来的多器官功能衰竭仍是外科重症监护病房的主要死亡原因。尽管人们已将大量精力集中在休克和脓毒症后大量释放的介质上，但对促炎细胞因子等介质的阻断尚未带来成功的治疗方法。然而，随着越来越多的研究问世，创伤性出血和脓毒症后导致细胞和器官功能障碍的机制正逐渐被更好地理解，目前正在评估一些有前景的新治疗方法。为了理解导致细胞功能障碍以及由此产生的不可逆器官损伤和多器官功能衰竭的确切机制，在细胞和亚细胞水平将各种病理生理变化与介质和信号转导途径联系起来很重要。在这篇综述中，我们首先关注创伤、失血性休克和脓毒症后导致细胞和器官功能障碍，尤其是肝细胞功能障碍的因素和介质。还将讨论信号转导途径的变化，特别是丝裂原活化蛋白激酶、转录因子、一氧化氮、热休克蛋白和炎性细胞因子在创伤性出血和脓毒症后细胞和器官功能障碍发展中的作用。此外，还包括在不利循环条件下改善细胞和器官功能的潜在治疗方法。
