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Volume 41 Issue 9
Sep.  2025
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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2025  >  41(9): 847-856
Zhang ZJ,Li DW,Liu LW,et al.Roles and mechanism of mitophagy in myocardial injury in mice following delayed resusafter severe burns[J].Chin J Burns Wounds,2025,41(9):847-856.DOI: 10.3760/cma.j.cn501225-20250514-00226.
Citation: Zhang ZJ,Li DW,Liu LW,et al.Roles and mechanism of mitophagy in myocardial injury in mice following delayed resusafter severe burns[J].Chin J Burns Wounds,2025,41(9):847-856.DOI: 10.3760/cma.j.cn501225-20250514-00226.
shu

Roles and mechanism of mitophagy in myocardial injury in mice following delayed resuscitation after severe burns

doi: 10.3760/cma.j.cn501225-20250514-00226
  • 1.

    Senior Department of Burns and Plastic Surgery, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China

  • 2.

    PLA Medical University, Beijing 100853, China

Funds:

National Key Research and Development Program 2024YFC3016604

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    Abstract
  •   Objective  To explore the roles and mechanism of mitophagy in myocardial injury in mice following delayed resuscitation after severe burns.  Methods  This study was an experimental study. Forty-five 6-8-week-old male C57BL/6J mice were divided into sham injury group, 0 h post-injury rehydration group, 3 h post-injury rehydration group, 6 h post-injury rehydration group, and no post-injury rehydration group, with 9 mice in each group, according to the random number table (the same grouping method below). The mice in sham injury group were subjected to a sham injury, while the mice in the remaining 4 groups were subjected to full-thickness scald (hereinafter referred to as burn) of 30% total body surface area. The mice in 0 h post-injury rehydration group, 3 h post-injury rehydration group, and 6 h post-injury rehydration group received rehydration starting from 0 (immediately), 3, and 6 h post-injury, respectively. The mice in sham injury group and no post-injury rehydration group did not receive rehydration after injury. At 12 h post-injury, the serum levels of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) were detected using an automated biochemical analyzer. Myocardial histopathological scoring was performed using Kishimoto scores after hematoxylin-eosin staining. The protein expressions of mitophagy-related proteins, including translocase of outer mitochondrial membrane 20 (TOM20), microtubule-associated protein 1 light chain 3B (LC3B), P62, and Beclin-1 in myocardial tissue were detected by Western blotting, and the ratio of LC3B-Ⅱ/LC3B-Ⅰ was calculated. Twenty-seven 6-8-week-old male C57BL/6J mice were divided into 6 h post-injury rehydration alone group, 6 h post-injury rehydration+3-methyladenine (3-MA) group, and 6 h post-injury rehydration+rapamycin group, with 9 mice in each group. One week before burn modeling, mice in 6 h post-injury rehydration+3-MA group and 6 h post-injury rehydration+rapamycin group were injected intraperitoneally with the mitophagy inhibitor 3-MA or mitophagy activator rapamycin. All the mice in 3 groups received rehydration starting from 6 h post-injury following severe burns. At 12 h post-injury, the serum levels of LDH and CK-MB were detected, myocardial histopathological scoring was performed, and the protein expressions of mitochondrial autophagy-related proteins were detected as before. The mitochondrial ultrastructure changes in myocardial tissue were observed under a transmission electron microscope after uranium-lead double staining, and Flameng scoring was performed.  Results  At 12 h post-injury, compared with those in 0 h post-injury rehydration group the serum levels of LDH and CK-MB in mice in 6 h post-injury rehydration group and no post-injury rehydration group were significantly increased (P<0.05). At 12 h post-injury, compared with that in 0 h post-injury rehydration group, the myocardial histopathological score in mice in sham injury group was significantly decreased (P<0.05), and the myocardial histopathological scores in mice in 3 h post-injury rehydration group, 6 h post-injury rehydration group, and no post-injury rehydration group were significantly increased (P<0.05). At 12 h post-injury, compared with those in 0 h post-injury rehydration group, the protein expression of Beclin-1 was significantly decreased (P<0.05), while the protein expressions of TOM20 and P62 were significantly increased (P<0.05) in myocardial tissue of mice in sham injury group; the protein expression of Beclin-1 was significantly increased (P<0.05), while the protein expressions of TOM20 and P62 were significantly decreased (P<0.05) in myocardial tissue of mice in 3 h post-injury rehydration group; the protein expressions of Beclin-1 and ratios of LC3B-Ⅱ/LC3B-Ⅰwere significantly increased (P<0.05), while the protein expressions of TOM20 and P62 were significantly decreased (P<0.05) in myocardial tissue of mice in 6 h post-injury rehydration group and no post-injury rehydration group. At 12 h post-injury, compared with those in 6 h post-injury rehydration alone group, the serum levels of LDH and CK-MB in mice in 6 h post-injury rehydration+3-MA group were significantly decreased (P<0.05), while the serum levels of LDH and CK-MB in mice in 6 h post-injury rehydration+rapamycin group were significantly increased (P<0.05). At 12 h post-injury, compared with that in 6 h post-injury rehydration alone group, the myocardial histopathological score in mice in 6 h post-injury rehydration+3-MA group was significantly decreased (P<0.05), while the myocardial histopathological score in mice in 6 h post-injury rehydration+rapamycin group was significantly increased (P<0.05). At 12 h post-injury, compared with those in 6 h post-injury rehydration alone group, the protein expression of Beclin-1 and ratio of LC3B-Ⅱ/LC3B-Ⅰ were significantly decreased (P<0.05), while the protein expressions of TOM20 and P62 were significantly increased (P<0.05) in myocardial tissue of mice in 6 h post-injury rehydration+3-MA group; the protein expression of Beclin-1 and ratio of LC3B-Ⅱ/LC3B-Ⅰwere significantly increased (P<0.05), while the protein expressions of TOM20 and P62 were significantly decreased (P<0.05) in myocardial tissue of mice in 6 h post-injury rehydration+rapamycin group. At 12 h post-injury, compared with 2.67±0.11 in 6 h post-injury rehydration alone group, the mitochondrial Flameng score (2.07±0.11) in myocardial tissue of mice in 6 h post-injury rehydration+3-MA group was significantly decreased (P<0.05), while the mitochondrial Flameng score (3.60±0.20) in myocardial tissue of mice in 6 h post-injury rehydration+rapamycin group was significantly increased (P<0.05).  Conclusions  Delayed rehydration leads to myocardial injury and excessive activation of mitophagy in mice with severe burns. The inhibition of mitophagy can mitigate myocardial injury caused by delayed rehydration after severe burns.

     

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