Artesunate protects sepsis model mice challenged with Staphylococcus aureus by decreasing TNF-α release via inhibition TLR2 and Nod2 mRNA expressions and transcription factor NF-κB activation
Artesunate protects sepsis model mice challenged with Staphylococcus aureus by decreasing TNF-α release via inhibition TLR2 and Nod2 mRNA expressions and transcription factor NF-κB activation
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DOI：
10.1016/j.intimp.2009.12.006
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发表时间：
2010-03-01
影响因子：
5.6
通讯作者：
Zhou, Hong
中科院分区：
文献类型：
--
作者：
Li, Bin;Li, Jun;Zhou, Hong
革兰氏阳性菌已成为引起脓毒症的最常见的微生物。金黄色葡萄球菌(S.金黄色葡萄球菌）是社区获得性感染和医院感染中的主要革兰氏阳性病原体。目的：探讨血吸虫病医院感染的病死率。金黄色葡萄球菌可以变化，但通常较高。本研究发现青蒿琥酯对小鼠热致死沙门氏菌的致死性攻击具有保护作用。以剂量依赖性方式。AS与氨苄西林钠-舒巴坦钠（AMPS）联合应用可进一步提高小鼠的存活率。金黄色葡萄球菌;而不是单独使用AMPS。这种保护作用与血清TNF-α水平降低有关。水平在体外实验中，AS预处理强烈抑制热灭活的S.金黄色葡萄球菌或肽聚糖。AS可下调热灭活的S.抑制热灭活金黄色葡萄球菌诱导的NF-κ B活化。金黄色。结论：AS对感染S.通过抑制TLR 2和Nod 2 mRNA表达和转录因子NF-κ B激活，金黄色葡萄球菌与其降低TNF-α释放有关。(C)2009由爱思唯尔公司出版
Gram-positive bacteria have become the most common Organisms responsible for the development of sepsis. Staphylococcus aureus (S. aureus) is the major gram-positive pathogen in both community-acquired and nosocomial infections. The Mortality associated with nosocomial infections caused by S. aureus may vary but are generally high. In the present study, we found that artesunate (AS) could protect mice against a lethal challenge with heat-killed S. aureus in a dose-dependent manner. and AS in combination with ampicillin sodium-sulbactam sodium (AMPS) Could further increase survival of mice challenged with live S. aureus; than AMPS alone. This protection was associated with reductions of serum at TNF-alpha. level. In in vitro experiments, AS-pretreatment strongly inhibited TNF-alpha release from murine peritoneal macrophage induced by heat-killed S. aureus or peptidoglycan in a dose-dependent manner. AS reduced the Toll like receptor 2 (TLR2) and nucleotide-binding oligomerization domain containing 2 (Nod2) mRNA expressions up-regulated by heat-killed S. aureus and inhibited NF-kappa B activation induced by heat-killed S. aureus. In conclusion, our results demonstrated that AS-mediated protection on septic mice challenged with S. aureus was associated with its reduction on TNF-alpha release via inhibition of TLR2 and Nod2 mRNA expressions and transcription factor NF-kappa B activation. (C) 2009 Published by Elsevier B.V.