Simulated aeromedical evacuation exacerbates burn induced lung injury: targeting mitochondrial DNA for reversal

Meng-Jing Xiao; Xiao-Fang Zou; Bin Li; Bao-Long Li; Shi-Jian Wu; Bo Zhang

doi:10.1186/s40779-021-00320-9

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Simulated aeromedical evacuation exacerbates burn induced lung injury: targeting mitochondrial DNA for reversal

RESEARCH | Updated：2023-02-28

- Simulated aeromedical evacuation exacerbates burn induced lung injury: targeting mitochondrial DNA for reversal
- Military Medical Research Vol. 9, Issue 1, Pages: 32-39(2022)
- Affiliations：
  
  1.Department of Burn and Plastic Surgery, Air Force Medical Center of Chinese PLA, Beijing 100142, China
  2.Department of Respiratory and Critical Care Medicine, Air Force Medical Center of Chinese PLA, Beijing 100142, China
- Author bio：
  
  * zoubai185@163.com;
  huxirenzhangb@163.com
- Funds：
- DOI：10.1186/s40779-021-00320-9
  CLC：
- Published：2022-02
- Accepted：
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Xiao et al.: Simulated aeromedical evacuation exacerbates burn induced lung injury: targeting mitochondrial DNA for reversal. Mil Med Res, 2021, 8: 30.
DOI：

Xiao et al.: Simulated aeromedical evacuation exacerbates burn induced lung injury: targeting mitochondrial DNA for reversal. Mil Med Res, 2021, 8: 30. DOI： 10.1186/s40779-021-00320-9.

摘要

Abstract

Background:

Aeromedical evacuation of patients with burn trauma is an important transport method in times of peace and war

during which patients are exposed to prolonged periods of hypobaric hypoxia; however

the effects of such exposure on burn injuries

particularly on burn-induced lung injuries

are largely unexplored. This study aimed to determine the effects of hypobaric hypoxia on burn-induced lung injuries and to investigate the underlying mechanism using a rat burn model.

Methods:

A total of 40 male Wistar rats were randomly divided into four groups (10 in each group): sham burn (SB) group

burn in normoxia condition (BN) group

burn in hypoxia condition (BH) group

and burn in hypoxia condition with treatment intervention (BHD) group. Rats with 30% total body surface area burns were exposed to hypobaric hypoxia (2000 m altitude simulation) or normoxia conditions for 4 h. Deoxyribonuclease I (DNase I) was administered systemically as a treatment intervention. Systemic inflammatory mediator and mitochondrial deoxyribonucleic acid (mtDNA) levels were determined. A histopathological evaluation was performed and the acute lung injury (ALI) score was determined. Malonaldehyde (MDA) content

myeloperoxidase (MPO) activity

and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome level were determined in lung tissues. Data among groups were compared using analysis of variance followed by Tukey’s test post hoc analysis.

Results:

Burns resulted in a remarkably higher level of systemic inflammatory cytokines and mtDNA release

which was further heightened by hypobaric hypoxia exposure (

0.01). Moreover

hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression

MDA content

and MPO activity in the lung (

0.05 or

0.01). Burn-induced lung injuries were exacerbated

as shown by the histopathological evaluation and ALI score (

0.01). Administration of DNase I markedly reduced mtDNA release and systemic inflammatory cytokine production. Furthermore

the NLRP3 inflammasome level in lung tissues was decreased and burn-induced lung injury was ameliorated (

0.01).

Conclusions:

Our results suggested that simulated aeromedical evacuation further increased burn-induced mtDNA release and exacerbated burn-induced inflammation and lung injury. DNase I reduced the release of mtDNA

limited mtDNA-induced systemic inflammation

and ameliorated burn-induced ALI. The intervening mtDNA level is thus a potential target to protect from burn-induced lung injury during aeromedical conditions and provides safer air evacuations for severely burned patients.

关键词

Keywords

references

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