1. Academic Validation
  2. Exenatide inhibits necrosis by enhancing angiogenesis and ameliorating ischemia/reperfusion injury in a random skin flap rat model

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

  • Int Immunopharmacol. 2021 Jan;90:107192. doi: 10.1016/j.intimp.2020.107192.
Ji-Bing He 1 Xin-Yi Ma 1 Wen-Jie Li 1 Ying-Ying Liu 1 Ding-Sheng Lin 2
Affiliations

Affiliations

  • 1 Department of Hand Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • 2 Department of Hand Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: lindingsheng@gmail.com.
Abstract

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 μg/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-1β, nuclear factor kappa beta (NF-κB), Toll-like Receptor 4 (TLR4), and tumor necrosis factor α (TNF-α). 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-1β, NF-κB, TLR4, and TNF-α), thereby promoting angiogenesis and inhibiting inflammation.

Conclusions: Exenatide potentially inhibits necrosis in our rat random skin FLAP model.

Keywords

Angiogenesis; Exenatide; Inflammation; Ischemia/reperfusion injury; Necrosis; Random skin flap.

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