SIRT1激动剂CAY10602对急性肝衰竭小鼠肝损伤保护作用研究*

doi:10.3969/j.issn.1672-5069.2025.01.006

Abstract

Abstract: Objective This experiment was performed to investigate protective effects of silencing information regulator 2 related enzyme 1 (SIRT1) agonist CAY10602 on liver injuries in mice with acute liver failure (ALF). Methods Forty mice were randomly divided into 5 groups, e.g., control, model, CAY10602-intervend, glycyrrhizin (GLY)-intervened and CAY10602 and GLY combination-intervened group, with 8 mice in each group. A model of ALF was established by intraperitoneal injection of lipopolysaccharide and D-galactosamine (LPS/D-Gal). SIRT1 agonist CAY10602 and high mobility group box-1 protein (HMGB1) inhibitor glycyrrhizin (GLY) were used for intervention. Hepatic expression of SIRT1, HMGB1, and ferroptosis-related protein glutathione peroxidase 4 (GPX4), and Acyl-CoA synthetase long-chain family member 4 (ACSL4) was detected by Western blot. Results Liver tissue structure of mice in LPS/D-Gal model group was seriously disordered, necrosis of hepatocytes was found, and liver tissue congestion was serious; However, SIRT1 agonist CAY10602 intervention could significantly ameliorate liver tissue injuries; serum ALT, AST and bilirubin levels in LPS/D-Gal model group mice were (3278.3±520.8) U/L, (2457.0±545.5) U/L and (96.4±16.5) μmol/L, significantly higher than in control group [(32.1±10.3) U/L, (67.8±12.8) U/L and (4.7±2.3) μmol/L, P<0.05]; serum ALT, AST and bilirubin levels in LPS-Gal/D/CAY10602-intervened group mice were significantly lower than in the model group; compared with in the model group, CAY10602 significantly decreased hepatic expression of HMGB1 (P <0.05), while promoted ferroptosis-related protein GPX4 expression, and decreased expression of ACSL4 (P<0.05), suggesting that SIRT1 agonist CAY10602 might alleviate liver injuries by inhibiting HMGB1 expression and reducing ferroptosis in liver tissues. Conclusions SIRT1 agonist CAY10602 can protect liver tissue injuries, and the mechanism might be involved inhibition of hepatic HMGB1 release and ferroptosis occurrence.

Key words: Acute liver failure, Silencing information regulator 2 related enzyme 1, High mobility group box-1 protein, Ferroptosis, Mice

Shen Qiyan, Zhang Long, Zhang Yanqiong, et al. Protection of CAY10602, a SIRT1 agonist, on liver injuries in mice with LPS/D-Gal-induced acute liver failure[J]. Journal of Practical Hepatology, 2025, 28(1): 20-23.

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Protection of CAY10602, a SIRT1 agonist, on liver injuries in mice with LPS/D-Gal-induced acute liver failure

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