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猪的多发创伤和失血性休克的肺部炎症反应和免疫调节。

Pulmonary inflammatory response and immunomodulation to multiple trauma and hemorrhagic shock in pigs.

机构信息

Institute for Lung Research, Universities of Giessen and Marburg Lung Center, German Center for Lung Research (DZL), Philipps University Marburg, Marburg, Germany.

Vascular Biology Section, Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, United States of America.

出版信息

PLoS One. 2022 Dec 7;17(12):e0278766. doi: 10.1371/journal.pone.0278766. eCollection 2022.

Abstract

BACKGROUND

Patients suffering from severe trauma experience substantial immunological stress. Lung injury is a known risk factor for the development of posttraumatic complications, but information on the long-term course of the pulmonary inflammatory response and treatment with mild hypothermia are scarce.

AIM

To investigate the pulmonary inflammatory response to multiple trauma and hemorrhagic shock in a porcine model of combined trauma and to assess the immunomodulatory properties of mild hypothermia.

METHODS

Following induction of trauma (blunt chest trauma, liver laceration, tibia fracture), two degrees of hemorrhagic shock (45 and 50%) over 90 (n = 30) and 120 min. (n = 20) were induced. Animals were randomized to hypothermia (33°C) or normothermia (38°C). We evaluated bronchoalveolar lavage (BAL) fluid and tissue levels of cytokines and investigated changes in microRNA- and gene-expression as well as tissue apoptosis.

RESULTS

We observed a significant induction of Interleukin (IL) 1β, IL-6, IL-8, and Cyclooxygenase-2 mRNA in lung tissue. Likewise, an increased IL-6 protein concentration could be detected in BAL-fluid, with a slight decrease of IL-6 protein in animals treated with hypothermia. Lower IL-10 protein levels in normothermia and higher IL-10 protein concentrations in hypothermia accompanied this trend. Tissue apoptosis increased after trauma. However, intervention with hypothermia did not result in a meaningful reduction of pro-inflammatory biomarkers or tissue apoptosis.

CONCLUSION

We observed signs of a time-dependent pulmonary inflammation and apoptosis at the site of severe trauma, and to a lower extent in the trauma-distant lung. Intervention with mild hypothermia had no considerable effect during 48 hours following trauma.

摘要

背景

患有严重创伤的患者会经历大量的免疫应激。肺损伤是发生创伤后并发症的已知危险因素,但关于肺部炎症反应的长期过程以及轻度低温治疗的信息却很少。

目的

在猪的联合创伤模型中研究多发性创伤和失血性休克引起的肺部炎症反应,并评估轻度低温的免疫调节特性。

方法

在诱导创伤(钝性胸部创伤、肝脏裂伤、胫骨骨折)后,通过 90 分钟(n = 30)和 120 分钟(n = 20)两次引发 45%和 50%的失血性休克。动物被随机分为低温(33°C)或常温(38°C)组。我们评估了支气管肺泡灌洗液(BAL)中的细胞因子和组织水平,并研究了 microRNA 和基因表达以及组织凋亡的变化。

结果

我们观察到肺组织中白细胞介素(IL)1β、IL-6、IL-8 和环氧化酶-2 mRNA 的显著诱导。同样,BAL 液中可检测到 IL-6 蛋白浓度增加,而低温治疗的动物中 IL-6 蛋白浓度略有下降。常温时 IL-10 蛋白水平较低,低温时 IL-10 蛋白浓度较高,与这一趋势一致。创伤后组织凋亡增加。然而,低温干预并没有导致促炎生物标志物或组织凋亡的显著减少。

结论

我们观察到严重创伤部位存在时间依赖性肺部炎症和细胞凋亡,而在创伤远隔部位则程度较轻。在创伤后 48 小时内,轻度低温干预没有明显效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4157/9728855/c00dd01e94db/pone.0278766.g001.jpg

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