Toll-like receptors 4 contribute to endothelial injury and inflammation in hemorrhagic shock in mice
Toll-like receptors 4 contribute to endothelial injury and inflammation in hemorrhagic shock in mice
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DOI：
10.1097/ccm.0b013e31819da805
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发表时间：
2009-05-01
影响因子：
8.8
通讯作者：
Tamion, Fabienne
中科院分区：
文献类型：
--
作者：
Benhamou, Ygal;Favre, Julie;Tamion, Fabienne
目的：失血性休克复苏（HS/R）通过引发先天免疫系统的细胞进行炎症反应而促进器官损伤。Toll样受体（TLR）在休克/复苏条件下的信号转导中起重要作用。由于促炎介质是HS/R诱导的肠系膜内皮损伤的关键事件，我们评估了TLR 4或TLR 2在这种情况下的作用。设计：实验室调查。设置：鲁昂大学医学院研究实验室。受试者：具有相同C57 BL/6背景的雄性野生型、TLR 4（-/-）和TLR 2（-/-）小鼠。干预措施：小鼠进行了30分钟的失血性休克，随后1小时复苏，肠系膜内皮功能障碍，微血管损伤，和TNF α的生产进行了assessed. Measures和主要结果：HS/R显着降低一氧化氮介导的肠系膜松弛诱导乙酰胆碱，评估离体肌电描记器。相比之下，在TLR 4缺陷小鼠中，HS/R不损害一氧化氮介导的对乙酰胆碱的反应。在TLR 2缺陷小鼠中未观察到保护作用。TLR 4-缺陷小鼠也表现出显着减少液体复苏和TNF α全身production.Conclusions：TLR 4有助于失血性休克后肠系膜内皮功能障碍。这种早期TLR 4诱导的血管损伤，可能是该疾病中发生的全身炎症反应的重要触发因素。(Crit Care Med 2009; 37：1724-1728）
Objective: Hemorrhagic shock followed by resuscitation (HS/R) promotes organ injury by priming cells of the innate immune system for inflammatory response. Toll-like receptors (TLRs) play an important role in signal transduction in shock/resuscitation conditions. Because proinflammatory mediators are a critical event in mesenteric endothelial injury induced by HS/R, we assessed the role of TLR4 or TLR2 in this setting.Design: Laboratory investigation.Setting: Research laboratory at Rouen University Medical School.Subjects: Male wild-type, TLR4(-/-) and TLR2(-/-) mice with the same C57BL/6 background.Interventions: Mice were submitted to 30 minutes hemorrhagic shock followed by 1 hour resuscitation, after which mesenteric endothelial dysfunction, microvascular injury, and TNF alpha production were assessed.Measurements and Main Results: HS/R markedly decreased nitric oxide-mediated mesenteric relaxations induced by acetylcholine, assessed ex vivo on a myograph. By contrast, in TLR4-deficient mice, HS/R did not impair the nitric oxide-mediated responses to acetylcholine. No protection was observed in TLR2-deficient mice. TLR4-deficient mice also displayed a significant reduction in fluid resuscitation and TNF alpha systemic production.Conclusions: TLR4 contributes to mesenteric endothelial dysfunction after hemorrhagic shock. This early TLR4-induced vascular injury, may be an important trigger of the systemic inflammatory response occurring in this disease. (Crit Care Med 2009; 37:1724-1728)