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Sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating NFKB3 expression via miR-9-5p
Hepatic ischemia/reperfusion (IR) injury is a critical contraindication of hepatobiliary surgery and results in severe liver damage. It is imperative to identify underlying pathophysiological mechanisms. In the current study, a rat model of liver IR was established to explore the mechanisms of sevof...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425234/ https://www.ncbi.nlm.nih.gov/pubmed/30906455 http://dx.doi.org/10.3892/etm.2019.7272 |
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author | Liao, Xingzhi Zhou, Siqi Zong, Jian Wang, Zhiping |
author_facet | Liao, Xingzhi Zhou, Siqi Zong, Jian Wang, Zhiping |
author_sort | Liao, Xingzhi |
collection | PubMed |
description | Hepatic ischemia/reperfusion (IR) injury is a critical contraindication of hepatobiliary surgery and results in severe liver damage. It is imperative to identify underlying pathophysiological mechanisms. In the current study, a rat model of liver IR was established to explore the mechanisms of sevoflurane during surgical intervention on IR. The detection of cytokines was performed using ELISA and reverse transcription-quantitative polymerase chain reaction and western blot assays were used to detect mRNA and protein expression levels, respectively. The target protein of microRNA (miR)-9-5p was identified by in vitro luciferase reporter assay. Cell apoptosis was detected by Annexin-V/propidium iodide and TUNEL staining assays. The results demonstrated that sevoflurane exerted protective effect against liver IR. Sevoflurane administration ameliorated a cytokine storm by decreasing serum levels of interleukin (IL)-1 and −6 and tumor necrosis factor (TNF)-α, and improved liver function was determined. IR-induced damage was mediated by an increase in transcription factor p65 expression and activation of the nuclear factor (NF)-κB signaling pathway, which were suppressed by sevoflurane treatment. In situ analysis predicted that NFKB3, encoding for p65, may be targeted by miR-9-5p and the hypothesis was verified by in vitro reporter assays using wild type and mutant sequences of the NFKB3 3′-untranslated region. Furthermore, pretreatment of hepatic tissue with a miR-9-5p mimic inhibited IR-associated injury as suggested by the decrease in the Suzuki score and decreased serum levels of TNF-α, IL-1 and IL-6. The results indicated that sevoflurane protected the liver from IR injury by increasing miR-9-5p expression and miR-9-5p may be a potential treatment target in IR. |
format | Online Article Text |
id | pubmed-6425234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-64252342019-03-22 Sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating NFKB3 expression via miR-9-5p Liao, Xingzhi Zhou, Siqi Zong, Jian Wang, Zhiping Exp Ther Med Articles Hepatic ischemia/reperfusion (IR) injury is a critical contraindication of hepatobiliary surgery and results in severe liver damage. It is imperative to identify underlying pathophysiological mechanisms. In the current study, a rat model of liver IR was established to explore the mechanisms of sevoflurane during surgical intervention on IR. The detection of cytokines was performed using ELISA and reverse transcription-quantitative polymerase chain reaction and western blot assays were used to detect mRNA and protein expression levels, respectively. The target protein of microRNA (miR)-9-5p was identified by in vitro luciferase reporter assay. Cell apoptosis was detected by Annexin-V/propidium iodide and TUNEL staining assays. The results demonstrated that sevoflurane exerted protective effect against liver IR. Sevoflurane administration ameliorated a cytokine storm by decreasing serum levels of interleukin (IL)-1 and −6 and tumor necrosis factor (TNF)-α, and improved liver function was determined. IR-induced damage was mediated by an increase in transcription factor p65 expression and activation of the nuclear factor (NF)-κB signaling pathway, which were suppressed by sevoflurane treatment. In situ analysis predicted that NFKB3, encoding for p65, may be targeted by miR-9-5p and the hypothesis was verified by in vitro reporter assays using wild type and mutant sequences of the NFKB3 3′-untranslated region. Furthermore, pretreatment of hepatic tissue with a miR-9-5p mimic inhibited IR-associated injury as suggested by the decrease in the Suzuki score and decreased serum levels of TNF-α, IL-1 and IL-6. The results indicated that sevoflurane protected the liver from IR injury by increasing miR-9-5p expression and miR-9-5p may be a potential treatment target in IR. D.A. Spandidos 2019-04 2019-02-13 /pmc/articles/PMC6425234/ /pubmed/30906455 http://dx.doi.org/10.3892/etm.2019.7272 Text en Copyright: © Liao et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Liao, Xingzhi Zhou, Siqi Zong, Jian Wang, Zhiping Sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating NFKB3 expression via miR-9-5p |
title | Sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating NFKB3 expression via miR-9-5p |
title_full | Sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating NFKB3 expression via miR-9-5p |
title_fullStr | Sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating NFKB3 expression via miR-9-5p |
title_full_unstemmed | Sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating NFKB3 expression via miR-9-5p |
title_short | Sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating NFKB3 expression via miR-9-5p |
title_sort | sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating nfkb3 expression via mir-9-5p |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425234/ https://www.ncbi.nlm.nih.gov/pubmed/30906455 http://dx.doi.org/10.3892/etm.2019.7272 |
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