Local injection of deferoxamine improves neovascularization in ischemic diabetic random flap by increasing HIF-1α and VEGF expression.

Abstract

Although the systemic administration of deferoxamine (DFO) is protective in experimental models of normal ischemic flap and diabetic wound, its effect on diabetic flap ischemia using a local injection remains unknown. To explore the feasibility of local injection of DFO to improve the survival of ischemic random skin flaps in streptozotocin (STZ)-induced diabetic mice. Ischemic random skin flaps were made in 125 mice. Animals were divided into the DFO-treated (n = 20), PBS-treated (n = 16) and untreated (n = 16) groups. Surviving area, vessel density, and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were evaluated on the seventh day after local injection. The viability of DFO-treated flap was significantly enhanced, with increased regional blood perfusion and capillary density compared with those in the two control groups. Fluorescence-activated cell sorting (FACS) analysis demonstrated a marked increase in systemic Flk-1+/CD11b- endothelial progenitor cells (EPCs) in DFO-treated mice. Furthermore, the expression of VEGF and HIF-1α was increased not only in diabetic flap tissue, but also in dermal fibroblasts cultured under hyperglycemic and hypoxic conditions. Local injection of DFO could exert preventive effects against skin flap necrosis in STZ-induced diabetic mice by elevating the expression of HIF-1α and VEGF, increased EPC mobilization, which all contributed to promote ischemic diabetic flap survival.