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Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice

BACKGROUND: Sepsis is a common disease that continues to increase in incidence in the world. Diseases, such as diabetes mellitus, may make the situation worse. Diabetic patients are at increased risk for common infections. This study was designed to investigate the role of glibenclamide on myocardia...

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Autores principales: Cai, Jian, Lu, Shuai, Yao, Zheng, Deng, Ya-Ping, Zhang, Ling-Di, Yu, Jia-Wen, Ren, Guo-Fei, Shen, Fu-Ming, Jiang, Guo-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147163/
https://www.ncbi.nlm.nih.gov/pubmed/25077824
http://dx.doi.org/10.1186/s12933-014-0106-y
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author Cai, Jian
Lu, Shuai
Yao, Zheng
Deng, Ya-Ping
Zhang, Ling-Di
Yu, Jia-Wen
Ren, Guo-Fei
Shen, Fu-Ming
Jiang, Guo-Jun
author_facet Cai, Jian
Lu, Shuai
Yao, Zheng
Deng, Ya-Ping
Zhang, Ling-Di
Yu, Jia-Wen
Ren, Guo-Fei
Shen, Fu-Ming
Jiang, Guo-Jun
author_sort Cai, Jian
collection PubMed
description BACKGROUND: Sepsis is a common disease that continues to increase in incidence in the world. Diseases, such as diabetes mellitus, may make the situation worse. Diabetic patients are at increased risk for common infections. This study was designed to investigate the role of glibenclamide on myocardial injury by lipopolysaccharides (LPS) in streptozotocin induced diabetic mice (STZ-mice). METHODS: LPS was used to induce endotoxemia in STZ-mice. Heart rate and mean arterial pressure were measured by MPA-HBBS. Serum epinephrine level was measured by enzyme-linked immunosorbent assays (ELISA). Myocardial injury was examined by light and transmission electron microscope and TUNEL staining. Macrophage infiltration was measured by immunohistochemistry. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in myocardial tissue and serum in STZ-mice, and in conditional medium of primary cultured peritoneal macrophages were determined by ELISA. Nalp3 and Caspase-1 protein levels were measured by Western blotting analysis. RESULTS: STZ administration decreased body weight and increased blood glucose in C57BL/6 mice. LPS injection caused decreases of heart rate and mean arterial pressure, and elevated serum epinephrine level in C57BL/6 mice. Compared with control mice without STZ treatment, LPS induced more severe myocardial injury and macrophage infiltration in STZ-mice, which was attenuated by pretreatment of glibenclamide. LPS stimulation enhanced the levels of IL-1β and TNF-α in both cardiac tissue and serum. Glibenclamide pretreatment significantly inhibited the serum levels of pro-inflammatory cytokines. Either high glucose or LPS increased the levels of IL-1β and TNF-α in the conditional medium of peritoneal macrophages. Glibenclamide treatment suppressed the increase of IL-1β level induced by high glucose and LPS. Furthermore, Nalp3 and Caspase-1 levels were markedly increased by high glucose plus LPS, and both proteins were significantly inhibited by glibenclamide treatment. CONCLUSIONS: We conclude that glibenclamide could attenuate myocardial injury induced by LPS challenge in STZ-mice, which was possibly related to inhibiting inflammation through Nalp3 inflammasomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-014-0106-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-41471632014-08-29 Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice Cai, Jian Lu, Shuai Yao, Zheng Deng, Ya-Ping Zhang, Ling-Di Yu, Jia-Wen Ren, Guo-Fei Shen, Fu-Ming Jiang, Guo-Jun Cardiovasc Diabetol Original Investigation BACKGROUND: Sepsis is a common disease that continues to increase in incidence in the world. Diseases, such as diabetes mellitus, may make the situation worse. Diabetic patients are at increased risk for common infections. This study was designed to investigate the role of glibenclamide on myocardial injury by lipopolysaccharides (LPS) in streptozotocin induced diabetic mice (STZ-mice). METHODS: LPS was used to induce endotoxemia in STZ-mice. Heart rate and mean arterial pressure were measured by MPA-HBBS. Serum epinephrine level was measured by enzyme-linked immunosorbent assays (ELISA). Myocardial injury was examined by light and transmission electron microscope and TUNEL staining. Macrophage infiltration was measured by immunohistochemistry. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in myocardial tissue and serum in STZ-mice, and in conditional medium of primary cultured peritoneal macrophages were determined by ELISA. Nalp3 and Caspase-1 protein levels were measured by Western blotting analysis. RESULTS: STZ administration decreased body weight and increased blood glucose in C57BL/6 mice. LPS injection caused decreases of heart rate and mean arterial pressure, and elevated serum epinephrine level in C57BL/6 mice. Compared with control mice without STZ treatment, LPS induced more severe myocardial injury and macrophage infiltration in STZ-mice, which was attenuated by pretreatment of glibenclamide. LPS stimulation enhanced the levels of IL-1β and TNF-α in both cardiac tissue and serum. Glibenclamide pretreatment significantly inhibited the serum levels of pro-inflammatory cytokines. Either high glucose or LPS increased the levels of IL-1β and TNF-α in the conditional medium of peritoneal macrophages. Glibenclamide treatment suppressed the increase of IL-1β level induced by high glucose and LPS. Furthermore, Nalp3 and Caspase-1 levels were markedly increased by high glucose plus LPS, and both proteins were significantly inhibited by glibenclamide treatment. CONCLUSIONS: We conclude that glibenclamide could attenuate myocardial injury induced by LPS challenge in STZ-mice, which was possibly related to inhibiting inflammation through Nalp3 inflammasomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-014-0106-y) contains supplementary material, which is available to authorized users. BioMed Central 2014-07-31 /pmc/articles/PMC4147163/ /pubmed/25077824 http://dx.doi.org/10.1186/s12933-014-0106-y Text en © Jian et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Original Investigation
Cai, Jian
Lu, Shuai
Yao, Zheng
Deng, Ya-Ping
Zhang, Ling-Di
Yu, Jia-Wen
Ren, Guo-Fei
Shen, Fu-Ming
Jiang, Guo-Jun
Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice
title Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice
title_full Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice
title_fullStr Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice
title_full_unstemmed Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice
title_short Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice
title_sort glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147163/
https://www.ncbi.nlm.nih.gov/pubmed/25077824
http://dx.doi.org/10.1186/s12933-014-0106-y
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