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Ischaemic preconditioning agents such as sevoflurane (Sevo) have been highlighted to play protective roles in hepatic I\/R injury. The current study aimed to investigate the molecular mechanism underlying the effects associated with Sevo in hepatic I\/R injury. Initially, mouse hepatic I\/R injury models were established <jats:italic>via<\/jats:italic> occlusion of the hepatic portal vein and subsequent reperfusion. The expression of forkhead box protein O4 (FOXO4) was detected using reverse transcription quantitative polymerase chain reaction and Western blot analysis from clinical liver tissue samples obtained from patients who had previously undergone liver transplantation, mouse I\/R models and oxygen\u2010deprived hepatocytes. The morphology of the liver tissues was analysed using haematoxylin\u2010eosin (HE) staining, with apoptosis detected <jats:italic>via<\/jats:italic> TUNEL staining. Immunohistochemistry methods were employed to identify the FOXO4\u2010positive cells. Mice with knocked out FOXO4 (FOXO4\u2010KO mice) were subjected to I\/R. In this study, we found FOXO4 was highly expressed following hepatic I\/R injury. After treatment with Sevo, I\/R modelled mice exhibited an alleviated degree of liver injury, fewer apoptotic cells and FOXO4\u2010positive cells. FOXO4 was a target gene of miR\u201096. Knockdown of FOXO4 could alleviate hepatic I\/R injury and decrease cell apoptosis. Taken together, the key observations of our study suggest that Sevo alleviates hepatic I\/R injury by means of promoting the expression of miR\u201096 while inhibiting FOXO4 expression. This study highlights the molecular mechanism mediated by Sevo in hepatic I\/R injury.<\/jats:p>","DOI":"10.1111\/jcmm.16063","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T02:02:04Z","timestamp":1622599324000},"page":"5899-5911","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sevoflurane alleviates hepatic ischaemia\/reperfusion injury by up\u2010regulating miR\u201096 and down\u2010regulating FOXO4"],"prefix":"10.1111","volume":"25","author":[{"given":"Binghua","family":"He","sequence":"first","affiliation":[{"name":"Jinan University  Guangzhou China"},{"name":"Department of Anesthesiology the Central Hospital of Shaoyang  Shaoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology the Central Hospital of Shaoyang  Shaoyang 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