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Bench to bedside review: therapeutic modulation of nitric oxide in sepsis—an update
Intensive Care Medicine Experimental Pub Date : 2019-12-01 , DOI: 10.1186/s40635-019-0274-x
Simon Lambden 1
Affiliation  

Nitric oxide is a signalling molecule with an extensive range of functions in both health and disease. Discovered in the 1980s through work that earned the Nobel prize, nitric oxide is an essential factor in regulating cardiovascular, immune, neurological and haematological function in normal homeostasis and in response to infection. Early work implicated exaggerated nitric oxide synthesis as a potentially important driver of septic shock; however, attempts to modulate production through global inhibition of nitric oxide synthase were associated with increased mortality. Subsequent work has shown that regulation of nitric oxide production is determined by numerous factors including substrate and co-factor availability and expression of endogenous regulators. In sepsis, nitric oxide synthesis is dysregulated with exaggerated production leading to cardiovascular dysfunction, bioenergetic failure and cellular toxicity whilst at the same time impaired microvascular function may be driven in part by reduced nitric oxide synthesis by the endothelium. This bench to bedside review summarises our current understanding of the ways in which nitric oxide production is regulated on a tissue and cellular level before discussing progress in translating these observations into novel therapeutic strategies for patients with sepsis.

中文翻译:

床边审查:脓毒症中一氧化氮的治疗调节——更新

一氧化氮是一种信号分子,在健康和疾病方面具有广泛的功能。一氧化氮是 1980 年代通过获得诺贝尔奖的工作发现的,它是调节心血管、免疫、神经和血液功能在正常体内平衡和对感染作出反应的重要因素。早期研究表明,过度的一氧化氮合成是感染性休克的潜在重要驱动因素;然而,通过全面抑制一氧化氮合酶来调节生产的尝试与死亡率增加有关。随后的工作表明,一氧化氮产生的调节由许多因素决定,包括底物和辅因子的可用性以及内源性调节剂的表达。在败血症中,一氧化氮合成失调,过度生成导致心血管功能障碍、生物能量衰竭和细胞毒性,同时微血管功能受损可能部分是由内皮细胞合成一氧化氮减少所致。在讨论将这些观察结果转化为脓毒症患者新治疗策略的进展之前,这篇床边综述总结了我们目前对组织和细胞水平上调节一氧化氮产生方式的理解。
更新日期:2019-12-01
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