Ethyl pyruvate: a novel treatment for sepsis.
Ethyl pyruvate: a novel treatment for sepsis.
复制标题
DOI：
10.1002/9780470059593.ch10
复制
发表时间：
2007
影响因子：
--
通讯作者：
M. Fink
中科院分区：
文献类型：
--
作者：
M. Fink
丙酮酸乙酯（EP）是一种来源于甘草酸的简单脂肪酸酯，即使在脓毒症发作后12-24小时才开始治疗，也能改善盲肠结扎和穿孔诱导的腹膜炎小鼠的存活率并改善器官系统功能障碍。在使用脂多糖刺激的RAW 264.7鼠巨噬细胞样细胞的研究中，EP抑制促炎转录因子NF-κ B的活化，并下调许多促炎细胞因子如肿瘤坏死因子（TNF）的分泌。在这种还原论体外系统中，EP还阻断了晚期出现的促炎性蛋白激酶样分子高迁移率族蛋白1（HMGB 1）的分泌。在内毒素血症或脓毒症小鼠模型中，EP治疗可降低TNF和HMGB 1的循环水平。虽然负责EP的有益作用的分子事件仍有待阐明，但一种机制可能涉及NF-κ B的p65组分中关键巯基残基的共价修饰。EP作为治疗人类脓毒症的治疗剂值得评价。
Ethyl pyruvate (EP), a simple aliphatic ester derived from pyruvic acid, improves survival and ameliorates organ system dysfunction in mice with peritonitis induced by caecal ligation and perforation, even when treatment is started as late as 12-24 hours after the onset of sepsis. In studies using lipopolysaccharide-stimulated RAW 264.7 murine macrophage like cells, EP inhibits activation of the pro-inflammatory transcription factor, NF-kappaB, and down regulates secretion of a number of pro-inflammatory cytokines, such as tumour necrosis factor (TNF). In this reductionist in vitro system, EP also blocks secretion of the late-appearing pro inflammatory cytokine-like molecule, high mobility group box 1 (HMGB1). In murine models of endotoxaemia or sepsis, treatment with EP decreases circulating levels of TNF and HMGB1. While the molecular events responsible for the salutary effects of EP remain to be elucidated, one mechanism may involve covalent modification of a critical thiol residue in the p65 component of NF-kappaB. EP warrants evaluation as a therapeutic agent for the treatment of sepsis in humans.