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Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion-induced acute lung injury by inhibiting autophagy in diabetic rats

Oxymatrine (OMT) is the primary active component of Sophora flavescens Ait., and is widely used for the treatment of diabetic complications. The present study aimed to investigate the effects of OMT on acute lung injury (ALI) in diabetic rats subjected to myocardial ischemia/reperfusion (I/R). ALI i...

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Autores principales: Xiong, Zhen, Xu, Jiali, Liu, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809908/
https://www.ncbi.nlm.nih.gov/pubmed/33398371
http://dx.doi.org/10.3892/mmr.2021.11822
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author Xiong, Zhen
Xu, Jiali
Liu, Xin
author_facet Xiong, Zhen
Xu, Jiali
Liu, Xin
author_sort Xiong, Zhen
collection PubMed
description Oxymatrine (OMT) is the primary active component of Sophora flavescens Ait., and is widely used for the treatment of diabetic complications. The present study aimed to investigate the effects of OMT on acute lung injury (ALI) in diabetic rats subjected to myocardial ischemia/reperfusion (I/R). ALI in a myocardial I/R model was established in streptozocin-induced diabetic rats. Enzyme-linked immunosorbent assays were used to evaluate the levels of creatine kinase isoenzyme MB and lactate dehydrogenase, and the inflammatory response was assessed via leukocyte counts and the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 in the bronchoalveolar lavage (BAL) fluid. Hematoxylin and eosin staining was used to determine pathological changes to the lung tissue, and the autophagy-related proteins LC-3II/LC-3I, Beclin-1, autophagy protein 5 (Atg5) and p62 were detected by western blotting. Diabetic rats subjected to myocardial I/R showed increased levels of ALI with a higher lung injury score and WET/DRY ratio, and lower partial pressure of oxygen. This was accompanied by aberrant autophagy, indicated by an increased LC-3II/LC-3I ratio, decreased p62 expression levels, increased Atg5 and beclin-1 expression levels, decreased superoxide dismutase activity and increased 15-F2t-isoprostane formation in lung tissues, as well as increased levels of leukocytes, TNF-α, IL-6 and IL-8 in the BAL fluid. Administration of the autophagy inducer rapamycin significantly accelerated these alterations, while the autophagy inhibitor 3-Methyladenine exerted the opposite effects. These results indicated that diabetic lungs are more vulnerable to myocardial I/R, which was associated with aberrant autophagy. Furthermore, oxymatrine was observed to reverse and alleviate ALI in diabetic rats with myocardial I/R in a concentration-dependent manner, the mechanism of which may be associated with the inhibition of autophagy.
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spelling pubmed-78099082021-01-21 Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion-induced acute lung injury by inhibiting autophagy in diabetic rats Xiong, Zhen Xu, Jiali Liu, Xin Mol Med Rep Articles Oxymatrine (OMT) is the primary active component of Sophora flavescens Ait., and is widely used for the treatment of diabetic complications. The present study aimed to investigate the effects of OMT on acute lung injury (ALI) in diabetic rats subjected to myocardial ischemia/reperfusion (I/R). ALI in a myocardial I/R model was established in streptozocin-induced diabetic rats. Enzyme-linked immunosorbent assays were used to evaluate the levels of creatine kinase isoenzyme MB and lactate dehydrogenase, and the inflammatory response was assessed via leukocyte counts and the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 in the bronchoalveolar lavage (BAL) fluid. Hematoxylin and eosin staining was used to determine pathological changes to the lung tissue, and the autophagy-related proteins LC-3II/LC-3I, Beclin-1, autophagy protein 5 (Atg5) and p62 were detected by western blotting. Diabetic rats subjected to myocardial I/R showed increased levels of ALI with a higher lung injury score and WET/DRY ratio, and lower partial pressure of oxygen. This was accompanied by aberrant autophagy, indicated by an increased LC-3II/LC-3I ratio, decreased p62 expression levels, increased Atg5 and beclin-1 expression levels, decreased superoxide dismutase activity and increased 15-F2t-isoprostane formation in lung tissues, as well as increased levels of leukocytes, TNF-α, IL-6 and IL-8 in the BAL fluid. Administration of the autophagy inducer rapamycin significantly accelerated these alterations, while the autophagy inhibitor 3-Methyladenine exerted the opposite effects. These results indicated that diabetic lungs are more vulnerable to myocardial I/R, which was associated with aberrant autophagy. Furthermore, oxymatrine was observed to reverse and alleviate ALI in diabetic rats with myocardial I/R in a concentration-dependent manner, the mechanism of which may be associated with the inhibition of autophagy. D.A. Spandidos 2021-03 2021-01-04 /pmc/articles/PMC7809908/ /pubmed/33398371 http://dx.doi.org/10.3892/mmr.2021.11822 Text en Copyright: © Xiong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Xiong, Zhen
Xu, Jiali
Liu, Xin
Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion-induced acute lung injury by inhibiting autophagy in diabetic rats
title Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion-induced acute lung injury by inhibiting autophagy in diabetic rats
title_full Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion-induced acute lung injury by inhibiting autophagy in diabetic rats
title_fullStr Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion-induced acute lung injury by inhibiting autophagy in diabetic rats
title_full_unstemmed Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion-induced acute lung injury by inhibiting autophagy in diabetic rats
title_short Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion-induced acute lung injury by inhibiting autophagy in diabetic rats
title_sort oxymatrine exerts a protective effect in myocardial ischemia/reperfusion-induced acute lung injury by inhibiting autophagy in diabetic rats
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809908/
https://www.ncbi.nlm.nih.gov/pubmed/33398371
http://dx.doi.org/10.3892/mmr.2021.11822
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