The ameliorative effects of a hypnotic bromvalerylurea in sepsis
The ameliorative effects of a hypnotic bromvalerylurea in sepsis
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DOI：
10.1016/j.bbrc.2015.02.111
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发表时间：
2015-04-03
影响因子：
3.1
通讯作者：
Tanaka, Junya
中科院分区：
文献类型：
--
作者：
Kikuchi, Satoshi;Nishihara, Tasuku;Tanaka, Junya
脓毒症是一种严重的病理事件，经常导致危重患者死亡。然而，没有批准的药物来治疗脓毒症，尽管许多药物的临床试验具有不同的目标。因此，应根据脓毒症的发病机制，寻找有效的治疗方法。我们最近观察到，一种古老的催眠药，溴戊脲（BU）抑制多种促炎和抗炎介质在LPS或干扰素-γ激活的肺泡和腹腔巨噬细胞（AM和PMs）的表达。采取BU对巨噬细胞的抗炎作用，我们挑战它对脓毒症大鼠已受到盲肠结扎和穿孔（CLP）。脓毒症大鼠每天两次皮下注射BU。CLP处理后7天，85%的给予溶媒的脓毒症大鼠死亡，而给予BU将死亡率降低至50%。脓毒症大鼠表现出多器官衰竭的症状;组织病理学分析、血气测试等显示呼吸、循环和肾脏系统衰竭。BU改善了这些症状。BU还能抑制脓毒症大鼠血清IL-6水平的升高以及IL-6 mRNA的表达。因此，BU可能是一种通过预防MOF的发生来改善脓毒症的新药物。(C)2015 Elsevier Inc. All rights reserved.
Sepsis is a severe pathologic event, frequently causing death in critically ill patients. However, there are no approved drugs to treat sepsis, despite clinical trials of many agents that have distinct targets. Therefore, a novel effective treatment should be developed based on the pathogenesis of sepsis. We recently observed that an old hypnotic drug, bromvalerylurea (BU) suppressed expression of many kinds of pro- and anti-inflammatory mediators in LPS- or interferon-gamma activated alveolar and peritoneal macrophages (AMs and PMs). Taken the anti-inflammatory effects of BU on macrophages, we challenged it to septic rats that had been subjected to cecum-ligation and puncture (CLP). BU was subcutaneously administered to septic rats twice per day. Seven days after CLP treatment, 85% of septic rats administrated vehicle had died, whereas administration of BU reduce the rate to 50%. Septic rats showed symptoms of multi-organ failure; respiratory, circulatory and renal system failures as revealed by histopathological analyses, blood gas test and others. BU ameliorated these symptoms. BU also prevented elevated serum-IL-6 level as well as IL-6 mRNA expression in septic rats. Collectively, BU might be a novel agent to ameliorate sepsis by preventing the onset of MOF. (C) 2015 Elsevier Inc. All rights reserved.