Continuous pressure exacerbates ischemia–reperfusion injury in minipigs through the AKT/eNOS signaling pathway
Year: 2025
Type: article
Abstract: BACKGROUND: Pressure ulcers are localized injuries to the skin and subcutaneous tissue, often forming over bony prominences due to prolonged pressure or shear forces. These ulcers pose a significant health challenge, affecting nearly 3 million adults and creating a substantial healthcare burden. OBJECTIVES: This study aimed to explore the pathological, inflammatory, fibrotic, and oxidative responses in skin subjected to ischemia-reperfusion injury (IRI) under different pressure conditions using a minipig model. MATERIALS AND METHODS: Male minipigs (5-6 months old, 25-30 kg) were used to simulate IRI through varying pressure durations and intensities. Pathological assessments included collagen fiber disruption and damage to hair follicles and sebaceous glands. Inflammatory and oxidative responses were measured by analyzing microvessel density, glutathione peroxidase, superoxide dismutase, Vascular endothelial growth factor (VEGF), VEGF receptor 2, Hypoxia-inducible factor-1α(HIF-1α), Interleukin-1β(IL-1β), IL-6, Matrix Metalloproteinase-9 (MMP-9), MMP-1, cleaved caspase-3, phosphorylation RAC-alpha serine/threonine-protein kinase/Protein kinase B (p-AKT), and phosphorylation Endothelial Nitric Oxide Synthase (p-eNOS) levels. RESULTS: Increasing pressure duration and intensity resulted in significant collagen fiber disruption and damage to hair follicles and sebaceous glands. There was a decline in microvessel density and levels of glutathione peroxidase, superoxide dismutase, VEGF, and VEGF receptor 2. Conversely, HIF-1α, IL-1β, IL-6, MMP-9, MMP-1, cleaved caspase-3, p-AKT, and p-eNOS levels increased. CONCLUSION: External mechanical forces exacerbate ischemia-reperfusion injury in pressure ulcers by intensifying oxidative stress, inflammation, and fibrosis, mainly through the activation of the AKT/eNOS pathway.
Authors: Lin Tao, Xiaolin Ma, Ying Yang, Heng Wang, Xiaorong Yang, Yanli Luo
Language: English
Subfield: Occupational Therapy
Field: Health Professions
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,190
Funder: Sichuan University
OpenAlex ID: W4416870368
