Volume 42 Issue 4
Apr.  2026
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Ma HD,Li QL,Sun HJ,et al.Effect and mechanism of hyperbaric oxygen on chronic wounds of full-thickness skin defects in rats[J].Chin J Burns Wounds,2026,42(4):393-402.DOI: 10.3760/cma.j.cn501225-20241220-00496.
Citation: Ma HD,Li QL,Sun HJ,et al.Effect and mechanism of hyperbaric oxygen on chronic wounds of full-thickness skin defects in rats[J].Chin J Burns Wounds,2026,42(4):393-402.DOI: 10.3760/cma.j.cn501225-20241220-00496.

Effect and mechanism of hyperbaric oxygen on chronic wounds of full-thickness skin defects in rats

doi: 10.3760/cma.j.cn501225-20241220-00496
Funds:

Guangxi Medical and Health Appropriate Technology Development, Promotion and Application Project S2023111

Guangxi Natural Science Foundation Project 2025JJH140056

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  •   Objective  To investigate the effect and mechanism of hyperbaric oxygen on chronic wounds of full-thickness skin defects in rats.  Methods  This study was designed as grouped experimental study. Forty 3-month-old male Sprague-Dawley rats were divided into control group, model group, hyperbaric oxygen group, and ferrostatin-1 group using a random number table method, with 10 rats in each group. Rats in control group only received full-thickness skin excision on the back. Rats in model group received an intramuscular injection of hydrocortisone acetate after full-thickness skin excision on the back to establish chronic wounds. In addition to full-thickness skin excision on the back and intramuscular injection of hydrocortisone acetate, rats in hyperbaric oxygen group and in ferrostatin-1 group received hyperbaric oxygen therapy and ferrostatin-1 intervention, respectively. After 7 days of treatment, the wound condition was observed and the wound healing rate was calculated. Hematoxylin-eosin staining was used to detect the pathological changes of wound tissue and scored. Transmission electron microscopy was used to observe the ultrastructure of fibroblasts (Fbs) in the wound tissue. Enzyme-linked immunosorbent assay was used to detect the expression levels of interleukin-1β (IL-1β), IL-6, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of MMP-1 (TIMP-1) in the wound tissue. Relevant kits were used to determine the content of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) in the wound tissue. Immunofluorescence and Western blotting were used to detect the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the wound tissue.  Results  After 7 days of treatment, the wounds in all groups of rats exhibited redness, swelling, and exudation, with the most pronounced ulceration observed in model group; the process of wound epithelialization of rats in model group was also significantly delayed compared with that in hyperbaric oxygen group, ferrostatin-1 group, and control group. After 7 days of treatment, the wound healing rates of rats in hyperbaric oxygen group, ferrostatin-1 group, and control group were significantly higher than that in model group (P<0.05). After 7 days of treatment, varying degrees of edema and inflammatory infiltration were observed in the wound tissue of rats in all groups, with the most severe changes being observed in model group. The histopathological scores of wound tissue of rats in hyperbaric oxygen group, ferrostatin-1 group, and control group were significantly higher than that in model group (P<0.05). After 7 days of treatment, the mitochondrial structure of Fbs in the wound tissue of rats in control group was intact. In model group, the Fbs mitochondria in the wound tissue of rats were shrunken, the mitochondrial cristae disappeared and the outer membrane of mitochondria ruptured. In hyperbaric oxygen group and ferrostatin-1 group, the Fbs mitochondrial damage in the wound tissue of rats was mild. After 7 days of treatment, compared with those in model group, the expression levels of IL-1β, IL-6, and MMP-9 in the wound tissue of rats in hyperbaric oxygen group, ferrostatin-1 group, and control group were significantly decreased (P<0.05), while the expression levels of TIMP-1 were significantly increased (P<0.05). After 7 days of treatment, compared with that in model group, the MDA content in the wound tissue of rats in hyperbaric oxygen group, ferrostatin-1 group, and control group was significantly decreased (P<0.05), while the content of GSH and SOD was significantly increased (P<0.05). After 7 days of treatment, immunofluorescence detection showed that the expression levels of Nrf2, SLC7A11, and GPX4 in the wound tissue of rats in model group were 10.1±1.4, 23.2±1.9, and 19.7±1.3, respectively, which were significantly lower than those in hyperbaric oxygen group (20.6±1.8, 32.9±1.7, and 31.6±3.0, respectively), ferrostatin-1 group (21.2±2.4, 31.1±2.7, and 32.2±1.2, respectively), and control group (27.8±1.6, 39.4±2.1, and 39.4±2.0, respectively), P<0.05; Western blotting detection revealed that the expression levels of Nrf2, SLC7A11, and GPX4 in the wound tissue of rats in model group were 0.72±0.06, 0.56±0.05, and 0.69±0.03, respectively, which were significantly lower than those in hyperbaric oxygen group (0.88±0.03, 0.90±0.07, and 0.85±0.06, respectively), ferrostatin-1 group (0.86±0.06, 0.77±0.09, and 0.87±0.03, respectively), and control group (0.90±0.04, 0.82±0.04, and 0.87±0.04, respectively), P<0.05.  Conclusions  Hyperbaric oxygen can effectively promote the healing of chronic wounds of full-thickness skin defects in rats, and its mechanism may be related to activating the expression of ferroptosis inhibitory molecules Nrf2, SLC7A11, and GPX4, thereby reducing inflammatory response and oxidative stress.

     

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