Paeoniflorin improves survival in LPS-challenged mice through the suppression of TNF-α and IL-1β release and augmentation of IL-10 production

Paeoniflorin improves survival in LPS-challenged mice through the suppression of TNF-α and IL-1β release and augmentation of IL-10 production
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DOI:
10.1016/j.intimp.2010.11.012
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发表时间:
2011-02-01
影响因子:
5.6
通讯作者:
Wang, Huadong
Wang, Huadong
中科院分区:
医学2区
文献类型:
--
作者:
Cao, Wenjuan;Zhang, Wei;Wang, Huadong

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脂多糖(LPS)在革兰氏阴性菌引起的脓毒症和多器官功能障碍综合征中起重要作用,目前仍是重症监护病房高死亡率的主要原因。尽管芍药苷(Pae)在小鼠中显示出抗炎作用和对免疫性肝损伤的保护作用,但尚不清楚Pae是否改善内毒素血症小鼠的存活。本研究的目的是确定Pae对脂多糖(LPS)处理的小鼠的死亡率、多器官功能障碍和细胞因子产生的影响。结果表明,Pae预处理可降低LPS攻击小鼠的死亡率,减轻肺、肾损伤,降低血清肌酐水平,改善心脏收缩功能。进一步的实验表明,Pae抑制LPS刺激的肿瘤坏死因子-α(TNF-α)和白细胞介素-1 β(IL-1 β)的释放,并促进LPS诱导的白细胞介素-10(IL-10)的产生。我们的研究结果表明,Pae保护小鼠免受致命的LPS攻击,至少部分,通过抑制TNF-α和IL-1 β的产生和加速IL-10的表达。(C)2010 Elsevier B. V.保留所有权利。
Lipopolysaccharide (LPS) plays an important role in Gram-negative bacteria-induced sepsis and multiple organ dysfunction syndrome, which are still the leading cause of high mortality in intensive care units. Although paeoniflorin (Pae) has reportedly exhibited anti-inflammatory effect and protection against immunological liver injury in mice, it is not known whether Pae improve survival in endotoxemic mice. The purpose of this study was to determine the effect of Pae on the mortality, multiple organ dysfunction and cytokine production in lipopolysaccharide (LPS)-treated mice. We found that pretreatment with Pae decreased mortality, reduced lung and kidney injury, decreased serum creatinine level and improve systolic function of heart in mice challenged with LPS. Further experiments showed that Pae inhibited LPS-stimulated tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) release and promoted LPS-induced interleukin-10 (IL-10) production. Our results indicate that Pae protects mice against lethal LPS challenge, at least in part, through inhibiting TNF-alpha and IL-1 beta production and accelerating IL-10 expression. (C) 2010 Elsevier B.V. All rights reserved.