PHYSIOLOGICAL AND IMMUNE-BIOLOGICAL CHARACTERIZATION OF A LONG-TERM MURINE MODEL OF BLUNT CHEST TRAUMA
PHYSIOLOGICAL AND IMMUNE-BIOLOGICAL CHARACTERIZATION OF A LONG-TERM MURINE MODEL OF BLUNT CHEST TRAUMA
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DOI：
10.1097/shk.0000000000000277
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发表时间：
2015-02-01
期刊：
影响因子：
3.1
通讯作者：
Wagner, Florian
中科院分区：
文献类型：
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作者：
Hafner, Sebastian;Wagner, Katja;Wagner, Florian
钝性胸部创伤会引起肺部和全身炎症。这种炎症反应的长期过程是否与肺功能的持续损害有关仍然是一个争论的问题。我们假设，尽管肺力学和气体交换正常化，但在钝性胸部创伤后的后期时间点，炎症生物标志物的增加可能仍然存在。麻醉的自主呼吸雄性C57 BL/6 J小鼠经历冲击波Y诱导的钝性胸部创伤或假手术。12和24小时后，测量血气和肺力学，以及血液、支气管肺泡灌洗（BAL）和组织细胞因子浓度（多重细胞因子试剂盒）;血红素加氧酶1（HO-1）、活化的半胱天冬酶-3、Bcl-x（L）和Bax表达（蛋白质印迹法）;核因子-κ B活化（电泳迁移率变动测定）;硝基酪氨酸形成;和嘌呤能（P2 XR 4和P2 XR 7）受体表达（免疫组织化学）。通过苏木精-伊红和高碘酸-希夫染色评估组织学损伤。高分辨率呼吸测定法允许评估隔膜活检中的线粒体呼吸。胸部创伤显著增加组织和BAL细胞因子水平，与HO-1，嘌呤能受体表达和组织硝基酪氨酸形成的显著增加相关。相比之下，假手术组和创伤组之间的肺力学、气体交换和组织学损伤没有显示出任何显著差异。在小鼠钝性胸部创伤后的稍后时间点，免疫应答的激活仍然存在。增加的局部炎症反应和保留的肺功能的不一致性可以通过免疫反应和肺功能的分离来解释，例如先前在实验性脓毒症后提出的。
Blunt chest trauma causes pulmonary and systemic inflammation. It is still a matter of debate whether the long-term course of this inflammatory response is associated with persistent impairment of lung function. We hypothesized that an increase of inflammatory biomarkers may still be present at later time points after blunt chest trauma, eventually, despite normalized lung mechanics and gas exchange. Anesthetized spontaneously breathing male C57BL/6J mice underwent a blast waveYinduced blunt chest trauma or sham procedure. Twelve and 24 h later, blood gases and lung mechanics were measured, together with blood, bronchoalveolar lavage (BAL), and tissue cytokine concentrations (multiplex cytokine kit); heme oxygenase 1 (HO-1), activated caspase-3, Bcl-x(L), and Bax expression (Western blotting); nuclear factor-kappa B activation (electrophoretic mobility shift assay); nitrotyrosine formation; and purinergic (P2XR4 and P2XR7) receptor expression (immunohistochemistry). Histological damage was assessed by hematoxylin and eosin and periodic acid-Schiff staining. High-resolution respirometry allowed assessing mitochondrial respiration in diaphragm biopsies. Chest trauma significantly increased tissue and BAL cytokine levels, associated with a significant increase in HO-1, purinergic receptor expression, and tissue nitrotyrosine formation. In contrast, lung mechanics, gas exchange, and histological damage did not show any significant difference between sham and trauma groups. Activation of the immune response remains present at later time points after murine blunt chest trauma. Discordance of the increased local inflammatory response and preserved pulmonary function may be explained by a dissociation of the immune response and lung function, such as previously suggested after experimental sepsis.