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脓毒症中的一氧化碳

Carbon monoxide in sepsis.

作者信息

Hoetzel Alexander, Dolinay Tamas, Schmidt Rene, Choi Augustine M K, Ryter Stefan W

机构信息

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, The University of Pittsburgh School of Medicine, MUH 628 NW, 3459 Fifth Ave, Pittsburgh, Pennsylvania 15213, USA.

出版信息

Antioxid Redox Signal. 2007 Nov;9(11):2013-26. doi: 10.1089/ars.2007.1762.

Abstract

Despite modern practices in critical care medicine, sepsis or systemic inflammatory response syndrome remains a leading cause of morbidity and mortality in the intensive care unit. Thus, the need to identify new therapeutic tools for the treatment of sepsis is urgent. In this context, carbon monoxide has become a promising therapeutic molecule that can potentially prevent uncontrolled inflammation in sepsis. In humans, carbon monoxide arises endogenously from the degradation of heme by heme oxygenase enzymes. Both endogenously synthesized and exogenously applied carbon monoxide can exert antiinflammatory and antiapoptotic effects in cells and tissues. Based on these properties, carbon monoxide, when applied at low concentration, conferred protection in a variety of cellular and rodent models of sepsis, and furthermore reduced morbidity and mortality in vivo. Therefore, application of carbon monoxide may have a major impact on the future of sepsis treatment. This review summarizes evidence for salutary effects of carbon monoxide in sepsis of various organs, including lung, heart, kidney, liver, and intestine, and discusses the potential translation of the data into human clinical trials.

摘要

尽管危重病医学有现代治疗方法,但脓毒症或全身炎症反应综合征仍是重症监护病房发病和死亡的主要原因。因此,迫切需要找到治疗脓毒症的新治疗手段。在这种背景下,一氧化碳已成为一种有前景的治疗分子,有可能预防脓毒症中不受控制的炎症。在人体内,一氧化碳由血红素加氧酶降解血红素内源性产生。内源性合成和外源性应用的一氧化碳均可在细胞和组织中发挥抗炎和抗凋亡作用。基于这些特性,低浓度应用的一氧化碳在多种脓毒症细胞和啮齿动物模型中具有保护作用,并且还降低了体内的发病率和死亡率。因此,一氧化碳的应用可能会对脓毒症治疗的未来产生重大影响。本综述总结了一氧化碳对包括肺、心脏、肾脏、肝脏和肠道在内的各种器官脓毒症有益作用的证据,并讨论了将这些数据转化为人体临床试验的可能性。

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