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大鼠单侧肺酸伤后 7 天肺部反应过程的特征。

Characterization of the seven-day course of pulmonary response following unilateral lung acid injury in rats.

机构信息

Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.

出版信息

PLoS One. 2018 Jun 4;13(6):e0198440. doi: 10.1371/journal.pone.0198440. eCollection 2018.

Abstract

BACKGROUND

Aspiration of gastric acid is an important cause of acute lung injury. The time course of the pulmonary response to such an insult beyond the initial 48 hours is incompletely characterized. The purpose of this study was to comprehensively describe the pulmonary effects of focal lung acid injury over a seven day period in both directly injured and not directly injured lung tissue.

METHODS

Male Wistar rats underwent left-endobronchial instillation with hydrochloric acid and were sacrificed at 4, 24, 48, 96 or 168 h after the insult. Healthy non-injured animals served as controls. We assessed inflammatory cell counts and cytokine levels in right and left lung lavage fluid and blood, arterial oxygen tension, alterations in lung histology, lung wet-to-dry weight ratio and differential lung perfusion.

RESULTS

Lung acid instillation induced an early strong inflammatory response in the directly affected lung, peaking at 4-24 hours, with only partial resolution after 7 days. A less severe response with complete resolution after 4 days was seen in the opposite lung. Alveolar cytokine levels, with exception of IL-6, only partially reflected the localization of lung injury and the time course of the functional and histologic alterations. Alveolar leucocyte subpopulations exhibited different time courses in the acid injured lung with persistent elevation of alveolar lymphocytes and macrophages. After acid instillation there was an early transient decrease in arterial oxygen tension and lung perfusion was preferentially distributed to the non-injured lung.

CONCLUSION

These findings provide a basis for further research in the field of lung acid injury and for studies exploring effects of mechanical ventilation on injured lungs. Incomplete recovery in the directly injured lung 7 days after acid instillation suggests that increased vulnerability and susceptibility to further noxious stimuli are still present at that time.

摘要

背景

胃酸吸入是急性肺损伤的一个重要原因。这种损伤在最初 48 小时后对肺部的影响时间过程尚不完全清楚。本研究的目的是全面描述局灶性肺酸损伤后 7 天内直接损伤和未直接损伤肺组织的肺部效应。

方法

雄性 Wistar 大鼠经左支气管内滴注盐酸,于损伤后 4、24、48、96 或 168 小时处死。健康未受伤动物作为对照。我们评估了右肺和左肺灌洗液及血液中的炎症细胞计数和细胞因子水平、动脉血氧分压、肺组织学改变、肺湿重/干重比和差异肺灌注。

结果

肺酸灌洗在直接受影响的肺中引起了早期强烈的炎症反应,在 4-24 小时达到高峰,7 天后仅部分缓解。对侧肺的反应较轻,4 天后完全缓解。肺泡细胞因子水平(除了 IL-6)仅部分反映了肺损伤的定位和功能及组织学改变的时间过程。肺泡白细胞亚群在酸损伤肺中表现出不同的时间过程,肺泡淋巴细胞和巨噬细胞持续升高。酸灌洗后,动脉血氧分压早期短暂下降,肺灌注优先分布于未损伤肺。

结论

这些发现为肺酸损伤领域的进一步研究以及探索机械通气对损伤肺的影响提供了基础。损伤后 7 天直接损伤肺未完全恢复表明此时肺对进一步有害刺激的易感性和易损性仍然存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/313b/5986146/64d34a850cd3/pone.0198440.g001.jpg

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