Nesfatin-1 regulates the HMGB1-TLR4-NF-κB signaling pathway to inhibit inflammation and its effects on the random skin flap survival in rats

Zhikai Jiang; Kaitao Wang; Yuting Lin; Taotao Zhou; Yi Lin; Jianpeng Chen; Qicheng Lan; Zhefeng Meng; Xuao Liu; Hang Lin; Dingsheng Lin

doi:10.1016/j.intimp.2023.110849

Nesfatin-1 regulates the HMGB1-TLR4-NF-κB signaling pathway to inhibit inflammation and its effects on the random skin flap survival in rats

Int Immunopharmacol. 2023 Nov;124(Pt A):110849. doi: 10.1016/j.intimp.2023.110849. Epub 2023 Aug 25.

Authors

Affiliations

¹ Department of Hand Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
² Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, The First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, China.
³ Department of Hand Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, China. Electronic address: lindingsheng@gmail.com.

PMID: 37633241
DOI: 10.1016/j.intimp.2023.110849

Abstract

Objective: Random skin flaps are often placed by plastic surgeons to treat limb deformities and dysfunction. Nesfatin-1 (NES) is a peptide that exerts angiogenic, anti-inflammatory, and anti-oxidant effects. We assessed the impact of NES on flap survival and the underlying mechanism.

Methods: We modified the McFarlane random skin flap rat model. Thirty-six male Sprague-Dawley rats were randomly divided into a control group (corn oil solution with DMSO), low-dose group (NES-L at 10 µg/kg/day), and high-dose group (NES-H at 20 µg/kg/day). On day 7 after surgery, average flap survival areas were calculated. Laser Doppler blood flow monitoring and lead oxide/gelatin angiography were used to evaluate blood perfusion and neovascularization, respectively. Flap histopathological status was evaluated by hematoxylin and eosin (H&E) staining. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Immunohistochemical techniques were used to evaluate the expression of angiogenetic and inflammatory factors.

Results: In the experimental groups, the mean skin flap survival areas and blood perfusion increased considerably. The SOD activities in the experimental groups increased and the MDA contents decreased. Immunohistochemically, VEGF expression was upregulated in the experimental groups and the expression levels of inflammatory factors decreased markedly.

Conclusion: NES inhibited ischemic skin flap necrosis, promoted angiogenesis, and reduced ischemia-reperfusion injury and inflammation. Inhibition of the inflammatory HMGB1-TLR4-NF-κB signal pathway, which reduced flap inflammation and oxidative stress, may explain the enhanced flap survival.

Keywords: HMGB1-TLR4-NF-κB; Inflammation; Nesfatin-1; Oxidative stress; Random skin flap.