The eNOS-induced leonurine's new role in improving the survival of random skin flap.

In reconstructive and plastic surgery, random skin flaps are commonly utilized to treat skin abnormalities produced by a variety of factors. Flap delay procedure is commonly used to reduce flap necrosis. Due to the limitations of various conditions, the traditional surgical improvement can't effectively alleviate the skin flap necrosis. And leonurine (Leo) has antioxidant and anti-inflammatory effects. In this study, we researched the mechanism underlying the influences of varied Leo concentrations on the survival rate of random skin flaps. Our results showed that after Leo treatment, tissue edema and necrosis of the flap were significantly reduced, while angiogenesis and flap perfusion were significantly increased. Through immunohistochemistry and Western blot, we proved that Leo treatment can upregulate the level of angiogenesis, while Leo treatment significantly reduced the expression levels of oxidative stress, apoptosis and inflammation. As a result, it can significantly improve the overall viability of the random skin flaps through the increase of angiogenesis, restriction of inflammation, attenuation of oxidative stress, and reduction of apoptosis. And this protective function was inhibited by LY294002 (a broad-spectrum inhibitor of PI3K) and L-NAME (NG- nitro-L-arginine methyl ester, a non-selective NOS inhibitor). All in all, Leo is an effective drug that can activate the eNOS via the PI3K/Akt pathway. By encouraging angiogenesis, preventing inflammation, minimizing oxidative stress, and lowering apoptosis, Leo can raise the survival rate of random skin flaps. The recommended concentration of Leo in this study was 30 mg/kg.