Inflammatory and apoptotic alterations in serum and injured tissue after experimental polytrauma in mice: Distinct early response compared with single trauma or “double-hit” injury
Inflammatory and apoptotic alterations in serum and injured tissue after experimental polytrauma in mice: Distinct early response compared with single trauma or “double-hit” injury
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DOI：
10.1097/ta.0b013e31827d5f1b
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发表时间：
2013-02
影响因子：
3.4
通讯作者：
S. Weckbach;Christoph Hohmann;Sonja Braumueller;S. Denk;Bettina Klohs;P. Stahel;F. Gebhard;M. Huber-Lang;Mario Perl
中科院分区：
文献类型：
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作者：
S. Weckbach;Christoph Hohmann;Sonja Braumueller;S. Denk;Bettina Klohs;P. Stahel;F. Gebhard;M. Huber-Lang;Mario Perl
多发伤导致脓毒症和多器官功能衰竭后免疫系统的确切改变知之甚少。因此，早期局部和全身炎症和凋亡反应的特点是在一个新的多发性创伤模型，并与单一或联合损伤后看到的变化进行比较。方法C57 BL/6小鼠随机分为两组，一组为钝性双侧胸部创伤（Tx），另一组为闭合性头部创伤（Tx），右侧股骨骨折（包括对侧软组织损伤），另一组为复合创伤（PTx）。2小时或6小时后，处死动物，评价全身和局部肺免疫应答（支气管肺泡灌洗[BAL]/血浆细胞因子、肺髓过氧化物酶[MPO]活性和肺泡毛细血管屏障功能障碍）以及肺/脑细胞凋亡（肺胱天蛋白酶3蛋白质印迹法、免疫组织化学和多形核白细胞[PMN]膜联蛋白V）。结果血红蛋白、PO2饱和度和pH在实验组之间没有差异。局部BAL细胞因子/趋化因子在几乎所有组中显著增加，包括Tx。在PTx的情况下，肺部的这种局部炎症反应没有进一步增强。在2小时时，除假手术组和单纯闭合性脑损伤组外，所有组均显示肺MPO活性增加。伤后6小时，肺组织MPO仍仅在PTx组增加。发现BAL蛋白水平增加，反映了创伤后6小时所有Tx组的肺渗漏增强。只有PTx后，中性粒细胞凋亡显着减少，而肺caspase 3和血浆白细胞介素6/角质形成细胞趋化因子（KC）显着增加。结论与单纯损伤相比，多种损伤联合应用可使全身炎症反应提前。有趣的是，只有在PTx后，而不是在单次或两次撞击后，肺细胞凋亡增加，PMN凋亡沿着肺中中性粒细胞的长期存在，这可能代表多发性创伤后肺损伤的可能病理机制。
BACKGROUND The exact alterations of the immune system after polytrauma leading to sepsis and multiple-organ failure are poorly understood. Thus, the early local and systemic inflammatory and apoptotic response was characterized in a new polytrauma model and compared with the alterations seen after single or combined injuries. METHODS Anesthetized C57BL/6 mice were subjected to either blunt bilateral chest trauma (Tx), closed head injury, right femur fracture including contralateral soft tissue injury, or a combination of injuries (PTx). After 2 hours or 6 hours, animals were sacrificed, and the systemic as well as the local pulmonary immune response (bronchoalveolar lavage [BAL]/plasma cytokines, lung myeloperoxidase [MPO] activity, and alveolocapillary barrier dysfunction) were evaluated along with lung/brain apoptosis (lung caspase 3 Western blotting, immunohistochemistry, and polymorphonuclear leukocytes [PMN] Annexin V). RESULTS Hemoglobin, PO2 saturation, and pH did not differ between the experimental groups. Local BAL cytokines/chemokines were significantly increased in almost all groups, which included Tx. There was no further enhancement of this local inflammatory response in the lungs in case of PTx. At 2 hours, all groups except sham and closed head injury alone revealed an increased activity of lung MPO. However, 6 hours after injury, lung MPO remained increased only in the PTx group. Increased BAL protein levels were found, reflecting enhanced lung leakage in all groups with Tx 6 hours after trauma. Only after PTx was neutrophil apoptosis significantly decreased, whereas lung caspase 3 and plasma interleukin 6/keratinocyte chemoattractant (KC) were substantially increased. CONCLUSION The combination of different injuries leads to an earlier systemic inflammatory response when compared with the single insults. Interestingly, only after PTx but not after single or double hits was lung apoptosis increased, and PMN apoptosis was decreased along with a prolonged presence of neutrophils in the lungs, which may therefore represent a possible pathomechanism for lung injury after polytrauma.