Saxagliptin promotes random skin flap survival

Area of Science:

• Regenerative Medicine
• Surgical Innovation
• Pharmacological Research

Background:

• Flap necrosis is a significant complication in flap transplantation surgery.
• Dipeptidyl peptidase-4 inhibitors, like saxagliptin, are explored for their potential therapeutic benefits.
• Understanding the mechanisms behind flap survival is crucial for improving surgical outcomes.

Purpose of the Study:

• To evaluate the efficacy of saxagliptin in promoting random skin flap survival.
• To investigate the underlying mechanisms by which saxagliptin influences flap survival.
• To assess the impact of saxagliptin on angiogenesis, oxidative stress, and inflammatory pathways.

Main Methods:

• A dorsal McFarlane flap model was utilized in 36 rats, divided into high-dose saxagliptin, low-dose saxagliptin, and control groups.
• Flap survival, blood perfusion (laser Doppler), and angiogenesis (angiography) were assessed.
• Histopathological analysis, oxidative stress markers (SOD, MDA), and expression of key proteins (VEGF, TNF-α, NLRP3, IL-6, IL-18, TLR4, IL-1β, caspase-1, NF-κB, GSDMD) were evaluated.

Main Results:

• Saxagliptin treatment resulted in significantly larger flap survival areas, improved blood perfusion, and enhanced neovascularization compared to controls.
• Histopathological examination revealed better flap tissue status in the saxagliptin-treated groups.
• Treatment with saxagliptin dose-dependently reduced oxidative stress, inflammation (NF-κB, TLR4, TNF-α, IL-6, IL-18, IL-1β), and pyroptosis markers, while increasing vascular endothelial growth factor (VEGF).

Conclusions:

• Saxagliptin demonstrates a significant therapeutic effect in promoting random skin flap survival.
• The drug's mechanism involves reducing oxidative stress and inflammation while promoting angiogenesis.
• Saxagliptin represents a promising pharmacological agent for improving outcomes in flap transplantation surgery.