Saxagliptin promotes random skin flap survival

Background: Flap necrosis is a common issue encountered in clinical flap transplantation surgery. Here, we assessed the effects of saxagliptin, a dipeptidyl peptidase-4 inhibitor, on flap survival and explored the underlying mechanisms.Methods: A dorsal McFarlane flap model was established in 36 rats, which were randomly divided into a highdose saxagliptin (HS) group (saxagliptin, 30 mg/kg/day, n = 12), low-dose saxagliptin (LS) group (saxagliptin, 10 mg/kg/day, n = 12), and control group (n = 12). On day 7, flap survival was examined by eye in six rats from each group, along with determination of blood perfusion by laser Doppler flowmetry and angiogenesis by angiography. The remaining rats were sacrificed for harvesting of flap tissue. The status of the flap tissue was examined histopathologically by staining with hematoxylin and eosin (H & E). Oxidative stress was evaluated by determination of superoxide dismutase (SOD) activity and malonaldehyde (MDA) content. Gasdermin D (GSDMD), vascular endothelial growth factor (VEGF), tumor necrosis factor-& alpha; (TNF-& alpha;), NOD-like receptor pyrin domain containing 3 (NLRP3), interleukin (IL)-6, IL-18, Toll-like receptor 4 (TLR4), IL-18, caspase-1, and nuclear factor-& kappa;B (NF-& kappa;B) expression were detected by immunohistochemical analysis.Results: The experimental group exhibited a larger area of flap survival, with more blood perfusion and neovascularization and better histopathological status than the control group. The degree of oxidative stress and the levels of NF-& kappa;B, TLR4, proinflammatory cytokines, and pyroptosis-associated protein were decreased in the experimental group, while the VEGF level was increased in a saxagliptin dose-dependent manner. Conclusion: Saxagliptin promotes random skin flap survival.