Effects of Natural and Recombinant Hirudin on VEGF Expression and Random Skin Flap Survival in a Venous Congested Rat Model

Abstract We aim to investigate the effects of locally injected natural and recombinant hirudin on vascular endothelial growth factor (VEGF) expression and flap survival in venous congested skin flaps using a rat model. A dorsal random skin flap (10 × 3 cm) was prepared on each of 30 Wistar rats to establish a venous congested model. The rats were randomly divided into 2 treatment groups [receiving subcutaneous injection of either natural hirudin (6 U) or recombinant hirudin (6 U)] and a control group, which received subcutaneous injection of physiologic saline. After treatment, skin flap survival rates were calculated. VEGF messenger RNA levels and VEGF-positive vessel density as a marker for VEGF levels were measured in the flaps during and after treatment. The skin flap VEGF messenger RNA levels increased in the natural hirudin-treated group. The VEGF-positive vessel density was increased in all 3 groups. Statistically significant increases of VEGF levels were observed in the natural and recombinant hirudin-treated groups compared with the control group ( P < 0.05). The skin flap survival rates were improved in both hirudin treated groups. Natural and recombinant hirudin can increase VEGF expression in random skin flaps, which can potentially improve random skin flap survival in rats through angio genic mechanisms. Our results showed that hirudin treatment led to an increase in VEGF expression in the congested skin flaps. Natural hirudin demonstrated more pronounced effects than recombinant hirudin. Further studies are needed to understand the specific mechanisms.