Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils

• DOI: 10.3892/etm.2022.11609
• Publication Date: 2022-09-14T12:11:32Z
• Authors: Chen Bai; Zhengchen Jiang; Hongxin Jiang; Shuna Yu; Ming Li; Fangfang Chu; Yaxin Sheng; Jianguo Li; Jiying Jiang; Wanzhen Li
• Keywords: HMGB1

Inflammation is one of the most crucial mechanism underlying hepatic ischemia-reperfusion injury (HIRI). Several studies have shown that Ac2-26, active N-terminal peptide Annexin A1, could modulate anti-inflammatory processes and protect organs from (IRI). However effects Ac2-26 on an HIRI model not been reported to date. The purpose present study was determine whether pretreatment hepatocytes against acute by inhibiting neutrophil infiltration through regulation high mobility group box protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. To this end, a total 72 adult C57BL/6 mice were randomly divided into sham operation (sham), (I/R), I/R + groups. established occluding branch pedicle left median liver lobes with atraumatic vascular clamp for 45 min, followed reperfusion 24 h. expression HMGB1, TLR4, NF-κB, IκBα lymphocyte antigen 6 complex locus G6D (Ly6G) detected using reverse transcription-quantitative PCR, western blotting immunohistochemical staining; serum levels HMGB1 evaluated enzyme-linked immunosorbent assay. Flow cytometry used detect proportion neutrophil. results indicated preconditioning rescued hepatocyte dysfunctions induced HIRI. In addition, associated significant increase in release, accompanied increased which significantly inhibited Ac2-26. Furthermore, phosphorylated (p)-NF-κB ratio p-NF-κB NF-κB markedly increased, while decreased compared those group; however, these reversed administration. Additionally, administration resulted low neutrophils Ly6G as well reduced myeloperoxidase activity. Taken together, serves protective role regulating HMGB1/TLR4/NF-κB pathway infiltration.