Random-pattern skin flap transplantation is a common procedure in plastic surgery, but its distal area usually incurs ischemia and necrosis. Resveratrol (Rev), a natural polyphenol primarily found in peanuts, grapes, and red wine, which exerts multi-bioactivity. In this study, forty-eight rats with the modified "McFarlane flap" model were divided into Control and Rev groups, which were treated with vehicle Control and Rev, respectively. After 7 days of continuous treatment and observation, ischemic flap tissues were harvested to evaluate angiogenesis, apoptosis, oxidative stress, and autophagy. It was observed a greater survival area of flaps, accompanied with reduced water content and stronger blood supply, in the Rev group than in the Control group. In addition, Rev upregulated the expression of MMP9, VEGF, and Cadherin5, indicating that Rev promotes angiogenesis in ischemic flaps. Moreover, Rev decreased the levels of Bax, CYC, and Caspase3, suggesting that it inhibits apoptosis. Besides, Rev increased the expression of SOD1, eNOS, HO1, the activities of SOD and GSH, and reduced the levels of MDA, which uncovers that it depresses oxidative stress in ischemic flaps. Finally, it increased the expression of Beclin1, LC3II, VPS34, and CTSD, and decreased SQSTM1/p62 levels, which reveals that it activates autophagy in the flaps. These results suggest that Rev promotes random skin flap survival through proangiogenic, antiapoptotic, and antioxidative effects; moreover, autophagy is activated in the process, which might be another underlying mechanism for the flap survival.
Keywords: Resveratrol; angiogenesis; apoptosis; autophagy; oxidative stress; random-pattern skin flap.