急性肝衰竭（ALF）以严重的肝功能障碍、快速进展和高死亡率为特点，在治疗上存在一定困难。研究发现，芥子硫醇（SFN）作为核因子E2相关因子2（NRF2）激动剂具有抗炎、抗氧化和抗癌作用，并对神经退行性疾病、癌症和肝纤维化具有一定的保护作用。本文旨在探讨SFN对ALF的保护作用及其可能的作用机制。使用脂多糖和D-半乳糖胺在体内外诱导肝损伤。依次使用NRF2激动剂SFN和组蛋白脱乙酰化酶6（HDAC6）抑制剂ACY1215观察SFN在ALF中的保护作用及可能的机制。检测细胞存活率、乳酸脱氢酶（LDH）、Fe2+、谷胱甘肽（GSH）和丙二醛（MDA）。通过Western blotting和免疫荧光检测HDAC6、NRF2、谷胱过氧化酶4（GPX4）、酰基-CoA合成酶长链家族成员4（ACSL4）和溶质载体家族7成员11（SLC7A11）的表达。结果显示SFN激活了NRF2。SFN在体内外能够下调LDH、Fe2+、MDA和ACSL4的表达，上调GSH、GPX4和SLC7A11的表达，表明SFN对铁死亡具有抑制效应。此外，SFN组中HDAC6表达下调，表明SFN能够在ALF中下调HDAC6的表达。使用HDAC6抑制剂ACY1215后，SFN进一步降低了HDAC6的表达并抑制了铁死亡，表明SFN可能通过调节HDAC6活性来抑制铁死亡。SFN对ALF具有保护作用，其机制可能包括通过调节HDAC6来减少铁死亡。请引用本文：张永强，史晨馨，张冬梅，张玲玉，王丽微，宫志军。NRF2激动剂硫醇通过调节HDAC6活性缓解急性肝衰竭中的铁死亡。中西医结合学报。2023；提前出版。版权所有 ©2023上海长海医院。由Elsevier B.V.出版。保留所有权利。

Acute liver failure (ALF) is characterized by severe liver dysfunction, rapid progression and high mortality and is difficult to treat. Studies have found that sulforaphane (SFN), a nuclear factor E2-related factor 2 (NRF2) agonist, has anti-inflammatory, antioxidant and anticancer effects, and has certain protective effects on neurodegenerative diseases, cancer and liver fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo. NRF2 agonist SFN and histone deacetylase 6 (HDAC6) inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, lactate dehydrogenase (LDH), Fe2+, glutathione (GSH) and malondialdehyde (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting and immunofluorescence.Our results show that NRF2 was activated by SFN. LDH, Fe2+, MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6. Please cite this article as: Zhang YQ, Shi CX, Zhang DM, Zhang LY, Wang LW, Gong ZJ. Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity. J Integr Med. 2023; Epub ahead of print.Copyright © 2023 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.