Exenatide inhibits necrosis by enhancing angiogenesis and ameliorating ischemia/reperfusion injury in a random skin flap rat model

Background: Random skin flaps are often used for plastic repair because they are convenient and flexible. However, necrosis of flaps is a common complication that may lead to disastrous consequences. Exenatide, a glucagon-like peptide 1 receptor agonist, can enhance angiogenesis and ameliorate ischemia/reperfusion injury. Our experiments explored random skin flap outcomes after its use. Methods: We established modified dorsal McFarlane flaps on 54 Sprague-Dawley rats and divided the rats into three groups (control, Exe-I, and Exe-II). We intraperitoneally injected either 4 or 8 mu g/kg/day exenatide into the rats of the Exe-I and Exe-II groups, respectively. On the seventh day after the operation, we measured the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Tissue sections were obtained for histopathological and immunohistochemical analyses, and we evaluated the expression of vascular endothelial growth factor (VEGF), interleukin (IL) 6, IL-1 beta, nuclear factor kappa beta (NF-kappa B), Toll-like receptor 4 (TLR4), and tumor necrosis factor alpha (TNF-alpha). We measured blood flow reconstruction and angiogenesis using laser Doppler blood flowmetry and lead oxide/gelatin angiography, respectively. Results: Exenatide increased the average survival area of the flap and improved microvascular density and blood flow intensity in a dose-dependent manner. Meanwhile, the SOD level was up-regulated and the MDA level down-regulated. Exenatide also enhanced the expression of VEGF and reduced the expression of inflammatory cytokines (IL-6, IL-1 beta, NF-kappa B, TLR4, and TNF-alpha), thereby promoting angiogenesis and inhibiting inflammation. Conclusions: Exenatide potentially inhibits necrosis in our rat random skin flap model.

Automated summary

The study showed that Exenatide can increase the survival area of random skin flaps, improve microvascular density and blood flow intensity, up-regulate SOD level, down-regulate MDA level, enhance VEGF expression, reduce expression of inflammatory cytokines, promote angiogenesis, and inhibit inflammation in a rat model.