Cargando…
Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate
High-mobility group box-1 (HMGB1) acts as a proinflammatory cytokine that triggers and amplifies the inflammation cascade following ischemia/reperfusion (I/R). Ethyl pyruvate (EP) has been reported to inhibit HMGB1 release in several I/R models. This study was designed to investigate the potential r...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353799/ https://www.ncbi.nlm.nih.gov/pubmed/25780465 http://dx.doi.org/10.3892/etm.2015.2290 |
_version_ | 1782360651323146240 |
---|---|
author | LIN, YUNLING CHEN, LIANGLONG LI, WEIWEI FANG, JUN |
author_facet | LIN, YUNLING CHEN, LIANGLONG LI, WEIWEI FANG, JUN |
author_sort | LIN, YUNLING |
collection | PubMed |
description | High-mobility group box-1 (HMGB1) acts as a proinflammatory cytokine that triggers and amplifies the inflammation cascade following ischemia/reperfusion (I/R). Ethyl pyruvate (EP) has been reported to inhibit HMGB1 release in several I/R models. This study was designed to investigate the potential role of HMGB1 in a rat myocardial I/R model and to determine the effect of EP. Male Sprague Dawley rats were subjected to 30 min myocardial ischemia and 48 h reperfusion. In protocol 1, the rats were assigned to one of four groups (n=16 per group): Phosphate-buffered saline (PBS) or recombinant human HMGB1 (rhHMGB1) at three different doses (1, 10 or 100 μg/kg). In protocol 2, the rats were also assigned to one of four groups (n=16 per group): Sham, control, EP and EP + rhHMGB1. EP (40 mg/kg) or rhHMGB1 (100 μg/kg) was injected intravenously prior to reperfusion. Hemodynamic measurements were performed, and myocardial infarct size (IS) was calculated. Western blotting was conducted to evaluate HMGB1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. In the protocol 1 rats, the IS was markedly increased in the rhHMGB1 (100 μg/kg) group compared with that in the PBS group, and this increase was accompanied by elevated levels of TNF-α and IL-6. In the protocol 2 rats, I/R resulted a 4.8-fold increase in HMGB1 expression with an increased IS and impaired cardiac function compared with the sham group. EP significantly inhibited the elevated HMGB1 level, suppressed the activated TNF-α and IL-6 and reduced cardiac dysfunction. This cardioprotection was abolished by rhHMGB1. In conclusion, accumulation of HMGB1 is deleterious to the heart following myocardial I/R. EP can exert a strong protective effect against myocardial I/R injury, and these benefits are associated with a reduction in HMGB1. |
format | Online Article Text |
id | pubmed-4353799 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-43537992015-03-16 Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate LIN, YUNLING CHEN, LIANGLONG LI, WEIWEI FANG, JUN Exp Ther Med Articles High-mobility group box-1 (HMGB1) acts as a proinflammatory cytokine that triggers and amplifies the inflammation cascade following ischemia/reperfusion (I/R). Ethyl pyruvate (EP) has been reported to inhibit HMGB1 release in several I/R models. This study was designed to investigate the potential role of HMGB1 in a rat myocardial I/R model and to determine the effect of EP. Male Sprague Dawley rats were subjected to 30 min myocardial ischemia and 48 h reperfusion. In protocol 1, the rats were assigned to one of four groups (n=16 per group): Phosphate-buffered saline (PBS) or recombinant human HMGB1 (rhHMGB1) at three different doses (1, 10 or 100 μg/kg). In protocol 2, the rats were also assigned to one of four groups (n=16 per group): Sham, control, EP and EP + rhHMGB1. EP (40 mg/kg) or rhHMGB1 (100 μg/kg) was injected intravenously prior to reperfusion. Hemodynamic measurements were performed, and myocardial infarct size (IS) was calculated. Western blotting was conducted to evaluate HMGB1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. In the protocol 1 rats, the IS was markedly increased in the rhHMGB1 (100 μg/kg) group compared with that in the PBS group, and this increase was accompanied by elevated levels of TNF-α and IL-6. In the protocol 2 rats, I/R resulted a 4.8-fold increase in HMGB1 expression with an increased IS and impaired cardiac function compared with the sham group. EP significantly inhibited the elevated HMGB1 level, suppressed the activated TNF-α and IL-6 and reduced cardiac dysfunction. This cardioprotection was abolished by rhHMGB1. In conclusion, accumulation of HMGB1 is deleterious to the heart following myocardial I/R. EP can exert a strong protective effect against myocardial I/R injury, and these benefits are associated with a reduction in HMGB1. D.A. Spandidos 2015-04 2015-02-13 /pmc/articles/PMC4353799/ /pubmed/25780465 http://dx.doi.org/10.3892/etm.2015.2290 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles LIN, YUNLING CHEN, LIANGLONG LI, WEIWEI FANG, JUN Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate |
title | Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate |
title_full | Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate |
title_fullStr | Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate |
title_full_unstemmed | Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate |
title_short | Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate |
title_sort | role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353799/ https://www.ncbi.nlm.nih.gov/pubmed/25780465 http://dx.doi.org/10.3892/etm.2015.2290 |
work_keys_str_mv | AT linyunling roleofhighmobilitygroupbox1inmyocardialischemiareperfusioninjuryandtheeffectofethylpyruvate AT chenlianglong roleofhighmobilitygroupbox1inmyocardialischemiareperfusioninjuryandtheeffectofethylpyruvate AT liweiwei roleofhighmobilitygroupbox1inmyocardialischemiareperfusioninjuryandtheeffectofethylpyruvate AT fangjun roleofhighmobilitygroupbox1inmyocardialischemiareperfusioninjuryandtheeffectofethylpyruvate |