Therapeutic potential of pravastatin for random skin flaps necrosis: involvement of promoting angiogenesis and inhibiting apoptosis and oxidative stress

Background: Random skin flap is frequently used in plastic and reconstructive surgery, but its distal part often occurs ischemia and necrosis. Pravastatin (Prava) with bioactivities of pro-angiogenesis, anti-apoptosis and anti-oxidative stress, may be beneficial for flap survival. Materials and methods: A modified McFarlane flap model was performed in Sprague-Dawley rats. The animals were divided into the Control and Prava groups and treated as follows: the Prava group was injected intraperitoneally with 2 mg/kg Prava for consecutive 7 days, and the Control group received an equal volume of vehicle daily. On day 7, the necrosis skin flaps were observed, while visualization of blood flow below the tissue surface was performed by Laser Doppler blood flow imaging (LDBFI). Then animals were euthanized, and levels of angiogenesis, apoptosis and oxidative stress were analyzed. Results: Prava decreased necrosis and edema of skin flaps compared with the Control group, with more blood flow in the flap under LDBFI. Prava treatment increased the mean vessels density, elevated the expression levels of angiogenic proteins (matrix metallopeptidase 9, vascular endothelial growth factor, Cadherin5) and antioxidant proteins (superoxide dismutase 1 (SOD1), endothelial nitric oxide synthase, heme oxygenase), and decreased the expression of apoptotic factors (BAX, CYC, Caspase3). In addition, malondialdehyde content was reduced, and glutathione level and SOD activity were increased in the skin flaps after treatment with Prava. Conclusion: Prava promotes survival of random skin flap through induction of angiogenesis, and inhibition of apoptosis and oxidative stress.