Effects of stromal cell derived factor-1 and CXCR4 on the promotion of neovascularization by hyperbaric oxygen treatment in skin flaps

Abstract

Hyperbaric oxygen (HBO) is known to increase the survival of skin flaps by promoting neovascularization; however, the detailed mechanisms involved are not fully understood. In the present study, we aimed to characterize the effects of HBO treatment on neovascularization and skin flap survival. We also analyzed the mechanisms associated with the expression of angiogenic molecules, such as stromal cell derived factor-1 (SDF‑1) and its specific receptor CXCR4, to assess the effects of SDF-1 and CXCR4 on the promotion of neovascularization by HBO treatment in skin flaps. The epigastric pedicle skin flap model was established in rats that were randomly divided into the following groups: i) sham‑operated (SH group); ii) ischemia followed by reperfusion and analysis on the third and fifth day (IR3d and IR5d groups, respectively) postoperatively; iii) ischemia followed by reperfusion, HBO treatment and analysis on the third and fifth day (HBO3d and HBO5d groups, respectively) postoperatively. In the two HBO groups, animals received 1 h of HBO treatment in a 2.0 ATA chamber with 100% O2 twice per day for 3 days and then daily for 2 consecutive days following surgery. On the postoperative third and fifth day, skin flap survival measurement, histological analysis, immunohistochemical staining and western blotting for SDF‑1 and CXCR4 expression, were performed. Compared with those of the IR groups, skin flap survival, microvessel density (MVD) and expression of SDF‑1 and CXCR4 proteins were significantly increased in the HBO groups. Pearson's correlation analysis demonstrated a positive correlation between MVD and the high expression of SDF‑1 and CXCR4 following HBO treatment. Results of this study suggested that the effects of HBO treatment in promoting neovascularization may be explained by the upregulation of SDF‑1 and CXCR4 expression in the skin flaps of rats.