Pyroptosis is a new necrosis pattern of hepatocyte during liver inflammation in acute liver failure (ALF). Histone deacetylase 2 (HDAC2) is associated with several pathological conditions in the liver system. The aim of this study is to investigate whether knockdown or pharmacological inhibition of HDAC2 could reduce the level of pyroptosis in ALF through ULK1-NLRP3-pyroptosis pathway. The role of HDAC2 on ULK1-NLRP3-pyroptosis pathway during ALF was detected in clinical samples. The mechanism was investigated in transfected cells or in ALF mouse model. The RNA-sequencing results revealed that ULK1 was a negative target regulatory molecule by HDAC2. During the process of pyroptosis, the HDAC2 exerted the antagonistic effect with ULK1 by the K68 acetylation site in L02 cells. Then the role of HDAC2 on ULK1-NLRP3-pyroptosis pathway in ALF mouse model was also detected. Moreover, the related molecules to ULK1-NLRP3-pyroptosis pathway were verified different expression in normal health donors and clinical ALF patients. HDAC2 in hepatocytes plays a pivotal role in an ULK1-NLRP3 pathway driven auto-amplification of pyroptosis in ALF. One of the important mechanisms is that inhibition HDAC2 to reduce pyroptosis may be by modulating the K68 lysine site of ULK1.

细胞焦亡是急性肝衰竭（ALF）肝脏炎症过程中肝细胞的一种新的坏死模式。组蛋白脱乙酰酶 2 (HDAC2) 与肝脏系统中的几种病理状况有关。本研究的目的是研究敲低或药理学抑制 HDAC2 是否可以通过 ULK1-NLRP3-细胞焦亡途径降低 ALF 细胞焦亡水平。在临床样本中检测到 HDAC2 在 ALF 期间对 ULK1-NLRP3-细胞焦亡途径的作用。该机制在转染细胞或 ALF 小鼠模型中进行了研究。RNA 测序结果显示 ULK1 是 HDAC2 的负靶调节分子。在细胞焦亡过程中，HDAC2通过L02细胞的K68乙酰化位点与ULK1发挥拮抗作用。然后还检测了 ALF 小鼠模型中 HDAC2 对 ULK1-NLRP3-pyroptosis 通路的作用。此外，ULK1-NLRP3-pyroptosis 通路的相关分子在正常健康供体和临床 ALF 患者中得到了不同的表达。肝细胞中的 HDAC2 在 ALF 中 ULK1-NLRP3 通路驱动的细胞焦亡自动放大中起着关键作用。其中一个重要机制是抑制 HDAC2 以减少细胞焦亡可能是通过调节 ULK1 的 K68 赖氨酸位点来实现的。