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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  >  > Accepted Manuscript
Zhang Hao,Guan Hao,Wang Yuhang,et al.Role and mechanism of ferroptosis in acute lung injury associated with combined burn-blast trauma in rats[J].Chin J Burns Wounds,2024,40(11):1-9.DOI: 10.3760/cma.j.cn501225-20240528-00199.
Citation: Zhang Hao,Guan Hao,Wang Yuhang,et al.Role and mechanism of ferroptosis in acute lung injury associated with combined burn-blast trauma in rats[J].Chin J Burns Wounds,2024,40(11):1-9.DOI: 10.3760/cma.j.cn501225-20240528-00199.
shu

Role and mechanism of ferroptosis in acute lung injury associated with combined burn-blast trauma in rats

doi: 10.3760/cma.j.cn501225-20240528-00199
  • 1.

    Henan Medical Key Laboratory for Research of Trauma and Orthopedics, the Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, China

  • 2.

    Department of Burns and Cutaneous Surgery, Burn Center of PLA, the First Affiliated Hospital of Air Force Medical University, Xi'an710032, China

Funds:

General Program of National Natural Science Foundation of China 82272268

The Open Research Fund of Henan Key Laboratory for Trauma and Orthopedics of Xinxiang Medical University HZKFKT20220503

More Information
  • Corresponding author: Ren Wenjie, Email: xxmu_rwj@163.com
  • Received Date: 2024-05-28
    Available Online: 2024-11-05
    Abstract
  •   Objective  To investigates the role and mechanism of ferroptosis in acute lung injury associated with combined burn-blast trauma in rats.  Methods  This was an experimental study. Twenty-four 8-week-old male Sprague-Dawley rats were randomly divided into control group and experimental group, each containing 12 animals. The rats in experimental group were anesthetized and treated with explosion to make the model of acute lung injury associated with combined burn-blast trauma, whereas the rats in control group underwent sham injury. Twenty-four hours post-injury, the pathological morphology of lung tissue was observed by hematoxylin-eosin staining and immunohistochemical staining methods. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in the supernatant of bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay. The arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2) of abdominal aortic blood were measured by automatic animal blood gas analyzer. The lung tissue was weighed and the dry-wet ratio was calculated. The total protein concentration in BALF was measured by bicinchoninic acid protein concentration determination kit. The levels of oxidative stress factors, such as reactive oxygen species, malondialdehyde, superoxide dismutase (SOD), glutathione, and ferrous ion in lung tissue homogenates of rats were detected by related kits. The expression of ferroptosis related molecule glutathione peroxidase 4 (GPX4), lipid peroxides related molecule 4-hydroxynonenal (4-HNE) and DNA oxidative damage related molecule 8-hydroxydeoxyguanosine (8-OHdG) in lung tissue were detected by immunofluorescence and immunohistochemistry methods. Mitochondrial morphology was observed under transmission electron microscopy.  Results  Twenty-four hours post-injury, the lung tissue structure of rats in control group was clear and complete, and the alveolar wall was normal; in experimental group, the lung tissue edema of rats was obvious, the alveolar wall became thicker, and the structure was not clear. Twenty-four hours post-injury, compared with those in control group, the levels of TNF-α, IL-1β, and IL-6 in BALF supernatant of experimental group were significantly increased (with t values of 3.96, 9.84, and 10.60, respectively, P<0.05); the dry-wet ratio of lung tissue, lung injury score, and total protein concentration in BALF of rats in experimental group were significantly increased (with t values of 6.91, 6.64, and 10.04, respectively, P<0.05), PaO2 of abdominal aortic blood decreased significantly (t=8.85, P<0.05) while PaCO2 did not change significantly (t=0.20, P>0.05); the levels of SOD and glutathione in the lung homogenate of rats in experimental group were significantly decreased (with t values of 4.36 and 8.56, respectively, P<0.05), while the average levels of reactive oxygen species, malondialdehyde, and ferrous ion were significantly increased (with t values of 11.55, 9.78, and 14.77, respectively, P<0.05). Twenty-four hours post-injury, immunofluorescence staining and immunohistochemical staining showed that the expression of GPX4 in lung tissue of rats in experimental group were 0.245±0.024 and 0.786±0.240, respectively, which were significantly lower than 1.000±0.305 and 1.000±0.200 in control group (with t values of 6.05 and 2.60, respectively, P<0.05). The expression values of 4-HNE in lung tissue of rats in experimental group were 5.93±1.05 and 2.21±0.23 by immunofluorescence and immunohistochemical staining, respectively, which were significantly higher than 1.00±0.29 and 1.00±0.23 in control group (with t values of 11.13 and 9.16, respectively, P<0.05). The expression values of 8-OHdG in lung tissues of rats in experimental group were 2.08±0.40 and 1.61±0.29 by immunofluorescence and immunohistochemical staining, respectively, which were significantly higher than 1.00±0.40 and 1.00±0.26 in control group (with t values of 4.72 and 3.87, respectively, P<0.05). Twenty-four hours post-injury, compared with that in control group, the density of the double membrane of mitochondria in the lung tissue cells of rats in experimental group increased, the outer membrane ruptured, and the crista decreased  Conclusions  In rats with acute lung injury associated with combined burn-blast trauma in rats, there is oxidative DNA damage in lung tissue cells, the imbalance of antioxidant system in lung tissue, and the expression of GPX4, the key molecule against ferroptosis, is decreased, suggesting that ferroptosis is involved in the pathophysiological process.

     

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