组蛋白去乙酰化酶抑制剂ACY1215通过调控PANoptosis表达保护小鼠急性肝衰竭研究

doi:10.3969/j.issn.1672-5069.2025.04.007

摘要/Abstract

摘要： 目的探讨组蛋白去乙酰化酶(HDAC)抑制剂ACY1215对急性肝衰竭(ALF)小鼠的保护作用及其可能的作用机制。方法将18只小鼠随机分为对照组、模型组和ACY1215处理组,每组6只,采用脂多糖(LPS)和D-氨基半乳糖(D-Gal)联合腹腔注射诱导小鼠ALF模型,常规行血生化和组织病理学检查,采用Western blot法检测PANoptosis相关蛋白受体相互作用丝氨酸苏氨酸激酶1(RIPK1)、气体衍生物D蛋白(GSDMD)、半胱天冬氨酸蛋白酶-3(Caspase-3)、Caspase-8、混合谱系激酶结构域蛋白(MLKL)表达。结果 ALF组小鼠肝组织出现实质细胞排列紊乱,片状细胞坏死,伴有大量血细胞渗出和炎症细胞浸润,而ACY1215干预组小鼠肝组织病理学损害较ALF组明显减轻;ALF组血清ALT、AST和TBIL水平分别为(3279.8±639.0)U/L、(2510.1±383.2)U/L和(85.5±6.8)μmol/L,而ACY1215干预组则分别为(987.6±254.3)U/L、(426.3±105.6)U/L和(38.1±8.9)μmol/L,差异显著(P<0.05); ALF组小鼠肝组织 PANoptosis相关蛋白RIPK1、GSDMD、Caspase-3、Caspase-8和MLKL表达较对照组显著增强(P<0.05),而ACY1215干预组小鼠肝组织PANoptosis相关蛋白表达较ALF组显著减弱(P<0.05)。结论组蛋白去乙酰化酶抑制剂ACY1215可能通过调控PANoptosis发挥保护ALF小鼠的作用。

关键词: 急性肝衰竭, 组蛋白去乙酰化酶抑制剂, ACY1215, PANoptosis

Abstract: Objective The purpose of this experiment was to investigate the protective effect of histone deacetylase (HDAC) inhibitor ACY1215 on acute liver failure (ALF) in mice and to explore its possible mechanism. Methods 18 mice were randomly divided into control, model and ACY1215-intervened group, with 6 in each. The ALF model was induced by intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). Liver tissue PANoptosis associated protein expression, such as receptor-interacting serine-threonine kinase 1(RIPK1), gas derivative D protein (GSDMD), Caspase-3, Caspase-8 and mixed lineage kinase domain protein (ML) were detected by Western blot. Results Liver histopathological examination showed that disordered intrahepatic parenchymal cell arrangement, with lamellar cell necrosis, a large number of blood cell exudation, and inflammatory cell infiltration in ALF group, while liver tissue damage alleviated in ACY1215-intervened group; serum ALT, AST and total bilirubin levels in ALF group were (3279.8±639.0)U/L,(2510.1±383.2)U/L and (85.5±6.8)μmol/L, while they all decreased to [(987.6±254.3)U/L, (426.3±105.6)U/L and (38.1±8.9)μmol/L, respectively, P<0.05] in ACY1215-intervened group; intrahepatic tissue PANoptosis-related protein, such as RIPK1, GSDMD, Caspase-3, Caspase-8 and MLKL intensified in ALF group, while they all obviously weakened in ACY1215-intervened group (P<0.05). Conclusion Histone deacetylase inhibitor ACY1215 could play a protective role in mice with ALF, probably by regulating PANoptosis-related protein expression.

Key words: Acute liver failure, Histone deacetylase inhibitors, ACY1215, PANoptosis

闫立春, 张锴, 梁小卫. 组蛋白去乙酰化酶抑制剂ACY1215通过调控PANoptosis表达保护小鼠急性肝衰竭研究[J]. 实用肝脏病杂志, 2025, 28(4): 505-508.

Yan Lichun, Zhang Kai, Liang Xiaowei. ACY1215, a histone deacetylase inhibitor, protects mice from acute liver failure by regulating liver tissue PANoptosis expression[J]. Journal of Practical Hepatology, 2025, 28(4): 505-508.

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