Lycopene attenuates ischemic-hypoxic injury in random skin flaps via the Nrf2/HO-1 signaling pathway

Random skin flaps are commonly used in plastic and reconstructive surgeries. However, one of the most serious postoperative complications is the necrosis of distal portion of flap, which is mainly caused by a lack of blood flow. The nuclear factor erythroid-2 related factor 2 (Nrf2) can directly regulate the activity of heme oxygenase-1 (HO-1). Previous studies have shown that the powerful antioxidant lycopene (Lyc) attenuates renal injury by mitigating inflammation and apoptosis, which aroused our interest as to whether Lyc could promote the survival of ischemic flaps. In this study, we focused on analyzing the mechanism of Lyc after ischemic-hypoxic injury to skin flaps. The potential targets and mechanisms of Lyc in the ischemic situation can be predicted by network pharmacological analysis. Our results showed that Lyc promotes angiogenesis and attenuates oxidative stress, inflammation, and apoptosis to improve the survival of random skin flaps. These findings could be attributed to the mediation and regulation of the Nrf2/HO-1 signaling pathway by Lyc, as the blocking effect of brusatol on this pathway effectively inhibited the abovementioned occurrences. In conclusion, our study sheds new light on the therapeutic potential and clinical application of Lyc in enhancing random skin flap viability.