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Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis
Ulinastatin exhibits anti-inflammatory activity and protects the heart from ischemia/reperfusion injury. However, whether ulinastatin has a protective effect in diabetic cardiomyopathy is yet to be elucidated. The aim of the present study was to investigate the protective effects of ulinastatin agai...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609313/ https://www.ncbi.nlm.nih.gov/pubmed/28962186 http://dx.doi.org/10.3892/etm.2017.4824 |
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author | Wang, Wen-Ke Lu, Qing-Hua Wang, Xin Wang, Ben Wang, Juan Gong, Hui-Ping Wang, Lin Li, Hao Du, Yi-Meng |
author_facet | Wang, Wen-Ke Lu, Qing-Hua Wang, Xin Wang, Ben Wang, Juan Gong, Hui-Ping Wang, Lin Li, Hao Du, Yi-Meng |
author_sort | Wang, Wen-Ke |
collection | PubMed |
description | Ulinastatin exhibits anti-inflammatory activity and protects the heart from ischemia/reperfusion injury. However, whether ulinastatin has a protective effect in diabetic cardiomyopathy is yet to be elucidated. The aim of the present study was to investigate the protective effects of ulinastatin against diabetic cardiomyopathy and its underlying mechanisms. A C57/BL6J mice model of diabetic cardiomyopathy was used and mice were randomly assigned to three groups: Control group, diabetes mellitus (DM) group and DM + ulinastatin treatment group. Cardiac function was assessed using echocardiography and the level of inflammatory cytokine high mobility group box 1 (HMGB1) expression was measured using histopathological examination and reverse transcription-quantitative polymerase chain reaction. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured using western blotting and ELISA. The apoptosis rate in the myocardium was assessed by TUNEL assay. Caspase-3 activation, expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated × (Bax) were measured using western blotting, as was the activity of the mitogen activated protein kinase (MAPK) signaling pathway. The results indicated that ulinastatin significantly improved cardiac function in mice with DM. Ulinastatin treatment significantly downregulated HMGB1, TNF-α and IL-6 expression (P<0.05) and significantly reduced the percentage of apoptotic cardiomyocytes (P<0.05) via reduction of caspase-3 activation and the ratio of Bax/Bcl-2 in diabetic hearts (P<0.05). In addition, ulinastatin attenuated the activation of the MAPK signaling pathway. In conclusion, ulinastatin had a protective effect against DM-induced cardiac dysfunction in a mouse model. This protective effect may be associated with the anti-inflammatory and anti-apoptotic abilities of ulinastatin via the MAPK signaling pathway. |
format | Online Article Text |
id | pubmed-5609313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-56093132017-09-28 Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis Wang, Wen-Ke Lu, Qing-Hua Wang, Xin Wang, Ben Wang, Juan Gong, Hui-Ping Wang, Lin Li, Hao Du, Yi-Meng Exp Ther Med Articles Ulinastatin exhibits anti-inflammatory activity and protects the heart from ischemia/reperfusion injury. However, whether ulinastatin has a protective effect in diabetic cardiomyopathy is yet to be elucidated. The aim of the present study was to investigate the protective effects of ulinastatin against diabetic cardiomyopathy and its underlying mechanisms. A C57/BL6J mice model of diabetic cardiomyopathy was used and mice were randomly assigned to three groups: Control group, diabetes mellitus (DM) group and DM + ulinastatin treatment group. Cardiac function was assessed using echocardiography and the level of inflammatory cytokine high mobility group box 1 (HMGB1) expression was measured using histopathological examination and reverse transcription-quantitative polymerase chain reaction. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured using western blotting and ELISA. The apoptosis rate in the myocardium was assessed by TUNEL assay. Caspase-3 activation, expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated × (Bax) were measured using western blotting, as was the activity of the mitogen activated protein kinase (MAPK) signaling pathway. The results indicated that ulinastatin significantly improved cardiac function in mice with DM. Ulinastatin treatment significantly downregulated HMGB1, TNF-α and IL-6 expression (P<0.05) and significantly reduced the percentage of apoptotic cardiomyocytes (P<0.05) via reduction of caspase-3 activation and the ratio of Bax/Bcl-2 in diabetic hearts (P<0.05). In addition, ulinastatin attenuated the activation of the MAPK signaling pathway. In conclusion, ulinastatin had a protective effect against DM-induced cardiac dysfunction in a mouse model. This protective effect may be associated with the anti-inflammatory and anti-apoptotic abilities of ulinastatin via the MAPK signaling pathway. D.A. Spandidos 2017-09 2017-07-19 /pmc/articles/PMC5609313/ /pubmed/28962186 http://dx.doi.org/10.3892/etm.2017.4824 Text en Copyright: © Wang 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 Wang, Wen-Ke Lu, Qing-Hua Wang, Xin Wang, Ben Wang, Juan Gong, Hui-Ping Wang, Lin Li, Hao Du, Yi-Meng Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis |
title | Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis |
title_full | Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis |
title_fullStr | Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis |
title_full_unstemmed | Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis |
title_short | Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis |
title_sort | ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609313/ https://www.ncbi.nlm.nih.gov/pubmed/28962186 http://dx.doi.org/10.3892/etm.2017.4824 |
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