HSPA12B attenuates acute lung injury during endotoxemia in mice
HSPA12B attenuates acute lung injury during endotoxemia in mice
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HSPA12B 可减轻小鼠内毒素血症期间的急性肺损伤。
DOI：
10.1016/j.intimp.2015.09.022
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发表时间：
2015-12-01
影响因子：
5.6
通讯作者：
Liu，Li
中科院分区：
文献类型：
--
作者：
Zhang，Xiaojin;Li，Jingjin;Liu，Li
急性肺损伤（ALI）是脓毒症/脓毒性休克的重要表现。热休克蛋白A12 B（HSPA 12 B）是一种内皮细胞表达的热休克蛋白，对脂多糖（LPS）诱导的心肌和内皮细胞炎症反应具有负性调节作用。然而，目前尚不清楚HSPA 12 B是否对脓毒症/脓毒性休克期间的ALI发挥保护作用。在这项研究中，我们用LPS处理HSPA 12 B转基因小鼠（Tg）和野生型同窝小鼠（WT）6 h，以诱导内毒素血症。LPS处理显著引起肺损伤，如WT小鼠肺中的微结构破坏、血管渗漏和中性粒细胞募集所证明的。然而，LPS诱导的肺损伤在Tg小鼠中显著减弱。此外，与WT小鼠相比，Tg小鼠肺中LPS诱导的细胞外信号调节激酶（ERK）活化以及细胞间粘附分子-1（ICAM-1）和环氧合酶-2（考克斯-2）的上调受到抑制。此外，与WT小鼠相比，Tg肺显示出显著较低水平的血管内皮生长因子（VEGF）。我们的研究结果表明，肺保护作用的HSPA 12 B对内毒素的挑战，这表明管理HSPA 12 B的表达可以作为一个潜在的治疗目标，在脓毒症/脓毒性休克的ALI。
Acute lung injury (ALI) is a critical manifestation of sepsis/septic shock. Heat shock protein A12B (HSPA12B), an endothelial cell–expressed heat shock protein, shows a negative regulation of lipopolysaccharide (LPS)-induced inflammation in myocardium and endothelial cells. However, it is unclear whether HSPA12B exerts protective effects against ALI during sepsis/septic shock. In this study, we treated HSPA12B transgenic mice (Tg) and wild type littermates (WT) with LPS for 6 h to induce endotoxemia. LPS treatment significantly caused pulmonary injuries as evidenced by microarchitecture destruction, vascular leakage and neutrophil recruitment in lungs of WT mice. However, the LPS-induced pulmonary injuries were significantly attenuated in Tg mice. Moreover, the LPS-induced activation of extracellular signal-regulated kinases (ERKs) and upregulation of intercellular adhesion molecule-1 (ICAM-1) and Cyclooxygenase-2 (Cox-2) were inhibited in Tg lungs compared with that in WT mice. Additionally, Tg lungs showed a significant lower level of vascular endothelial growth factor (VEGF) compared with WT mice. Our results demonstrate a pulmonary protective effect of HSPA12B against endotoxin challenge, which indicates management of HSPA12B expression could serve as a potential therapeutic target for ALI during sepsis/septic shock.