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Sevoflurane alleviates hepatic ischaemia/reperfusion injury by up‐regulating miR‐96 and down‐regulating FOXO4
Hepatic ischaemia/reperfusion (I/R) injury represents an event characterized by anoxic cell death and an inflammatory response, that can limit the treatment efficacy of liver surgery. Ischaemic preconditioning agents such as sevoflurane (Sevo) have been highlighted to play protective roles in hepati...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256341/ https://www.ncbi.nlm.nih.gov/pubmed/34061461 http://dx.doi.org/10.1111/jcmm.16063 |
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author | He, Binghua Yang, Fan Ning, Yingxia Li, Yalan |
author_facet | He, Binghua Yang, Fan Ning, Yingxia Li, Yalan |
author_sort | He, Binghua |
collection | PubMed |
description | Hepatic ischaemia/reperfusion (I/R) injury represents an event characterized by anoxic cell death and an inflammatory response, that can limit the treatment efficacy of liver surgery. 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 via 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‐deprived hepatocytes. The morphology of the liver tissues was analysed using haematoxylin‐eosin (HE) staining, with apoptosis detected via TUNEL staining. Immunohistochemistry methods were employed to identify the FOXO4‐positive cells. Mice with knocked out FOXO4 (FOXO4‐KO 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‐positive cells. FOXO4 was a target gene of miR‐96. 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‐96 while inhibiting FOXO4 expression. This study highlights the molecular mechanism mediated by Sevo in hepatic I/R injury. |
format | Online Article Text |
id | pubmed-8256341 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82563412021-07-12 Sevoflurane alleviates hepatic ischaemia/reperfusion injury by up‐regulating miR‐96 and down‐regulating FOXO4 He, Binghua Yang, Fan Ning, Yingxia Li, Yalan J Cell Mol Med Original Articles Hepatic ischaemia/reperfusion (I/R) injury represents an event characterized by anoxic cell death and an inflammatory response, that can limit the treatment efficacy of liver surgery. 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 via 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‐deprived hepatocytes. The morphology of the liver tissues was analysed using haematoxylin‐eosin (HE) staining, with apoptosis detected via TUNEL staining. Immunohistochemistry methods were employed to identify the FOXO4‐positive cells. Mice with knocked out FOXO4 (FOXO4‐KO 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‐positive cells. FOXO4 was a target gene of miR‐96. 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‐96 while inhibiting FOXO4 expression. This study highlights the molecular mechanism mediated by Sevo in hepatic I/R injury. John Wiley and Sons Inc. 2021-06-01 2021-07 /pmc/articles/PMC8256341/ /pubmed/34061461 http://dx.doi.org/10.1111/jcmm.16063 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles He, Binghua Yang, Fan Ning, Yingxia Li, Yalan Sevoflurane alleviates hepatic ischaemia/reperfusion injury by up‐regulating miR‐96 and down‐regulating FOXO4 |
title | Sevoflurane alleviates hepatic ischaemia/reperfusion injury by up‐regulating miR‐96 and down‐regulating FOXO4 |
title_full | Sevoflurane alleviates hepatic ischaemia/reperfusion injury by up‐regulating miR‐96 and down‐regulating FOXO4 |
title_fullStr | Sevoflurane alleviates hepatic ischaemia/reperfusion injury by up‐regulating miR‐96 and down‐regulating FOXO4 |
title_full_unstemmed | Sevoflurane alleviates hepatic ischaemia/reperfusion injury by up‐regulating miR‐96 and down‐regulating FOXO4 |
title_short | Sevoflurane alleviates hepatic ischaemia/reperfusion injury by up‐regulating miR‐96 and down‐regulating FOXO4 |
title_sort | sevoflurane alleviates hepatic ischaemia/reperfusion injury by up‐regulating mir‐96 and down‐regulating foxo4 |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256341/ https://www.ncbi.nlm.nih.gov/pubmed/34061461 http://dx.doi.org/10.1111/jcmm.16063 |
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