Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy

In plastic and reconstructive surgery, random-skin flaps replantation have been commonly used to repair skin defects. However, flap necrosis due to ischemia and IR injury, limit clinical applications. Betulinic acid (BA), a pentacyclic triterpene of plant origin, may facilitate the survival of flaps. In the present study, the effects of BA on flap survival and the underlying mechanisms were assessed.Forty-eight mice with “McFarlane flap” model were randomly divided into Control, BA groups and BA+3MA groups, which were administrated with vehicle Control, BA, 3MA and BA. On a postoperative day 7, flap tissues were acquired to assess angiogenesis, apoptosis, oxidative stress, and autophagy. Our results showed that BA promoted the random skin flaps survival area, reduced tissue edema, and enhanced the number of microvessels. Besides, enhanced angiogenesis, attenuated apoptosis, alleviated oxidative stress and activated autophagy. However, the effects of BA on flap vitality and angiogenesis, apoptosis and oxidative stress were reversed by the inhibition of autophagy. Our finding revealed that BA improves the survival of random skin flaps, via promoting angiogenesis, dampening apoptosis and alleviating oxidative stress, which is mediated by activation of autophagy.