Department of Burn and Plastic Surgery, Air Force Medical Center of Chinese PLA, Beijing, 100142, China.
Department of Respiratory and Critical Care Medicine, Air Force Medical Center of Chinese PLA, Beijing, 100142, China.
Mil Med Res. 2021 May 13;8(1):30. doi: 10.1186/s40779-021-00320-9.
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.
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.
Burns resulted in a remarkably higher level of systemic inflammatory cytokines and mtDNA release, which was further heightened by hypobaric hypoxia exposure (P < 0.01). Moreover, hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression, MDA content, and MPO activity in the lung (P < 0.05 or P < 0.01). Burn-induced lung injuries were exacerbated, as shown by the histopathological evaluation and ALI score (P < 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 (P < 0.01).
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.
在和平与战争时期，航空医疗后送是治疗烧伤患者的重要手段，在此期间，患者会暴露于长时间的低气压低氧环境中；然而，这种暴露对烧伤的影响，特别是对烧伤引起的肺损伤的影响，在很大程度上尚未得到探索。本研究旨在使用大鼠烧伤模型确定低气压低氧对烧伤引起的肺损伤的影响，并探讨其潜在机制。
将 40 只雄性 Wistar 大鼠随机分为四组（每组 10 只）：假烧伤（SB）组、常压条件下烧伤（BN）组、低氧条件下烧伤（BH）组和低氧条件下烧伤并给予治疗干预（BHD）组。30%总体表面积烧伤的大鼠暴露于低气压低氧（2000 米海拔模拟）或常氧条件下 4 小时。系统给予脱氧核糖核酸酶 I（DNase I）作为治疗干预。测定系统炎症介质和线粒体脱氧核糖核酸（mtDNA）水平。进行组织病理学评估并确定急性肺损伤（ALI）评分。测定肺组织中丙二醛（MDA）含量、髓过氧化物酶（MPO）活性和核苷酸结合寡聚结构域样受体家族富含亮氨酸重复结构域 3（NLRP3）炎性体水平。使用方差分析比较组间数据，然后进行 Tukey 事后检验分析。
烧伤导致全身炎症细胞因子和 mtDNA 释放水平显著升高，低气压低氧暴露进一步加剧了这种升高（P<0.01）。此外，低气压低氧暴露导致肺组织中 NLRP3 炎性体表达、MDA 含量和 MPO 活性增加（P<0.05 或 P<0.01）。组织病理学评估和 ALI 评分显示，烧伤引起的肺损伤加重（P<0.01）。DNase I 显著减少 mtDNA 释放和全身炎症细胞因子的产生。此外，肺组织中 NLRP3 炎性体水平降低，烧伤引起的肺损伤得到改善（P<0.01）。
我们的研究结果表明，模拟航空医疗后送进一步增加了烧伤引起的 mtDNA 释放，并加重了烧伤引起的炎症和肺损伤。DNase I 减少 mtDNA 的释放，限制 mtDNA 诱导的全身炎症，并改善烧伤引起的 ALI。因此，mtDNA 水平的干预可能是在航空条件下保护烧伤引起的肺损伤的潜在靶点，并为严重烧伤患者提供更安全的空中后送。
