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Lycium barbarum polysaccharide protects rats and cardiomyocytes against ischemia/reperfusion injury via Nrf2 activation through autophagy inhibition

The irreversible loss of cardiomyocytes is mainly the result of ischemic/reperfusion (I/R) myocardial injury, leading to persistent heart dysfunction and heart failure. It has been reported that Lycium barbarum polysaccharide (LBP) has protective effects on cardiomyocytes, but the specific mechanism...

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Autores principales: Pan, Hao, Niu, Lin, Wu, Yihao, Chen, Liuying, Zhou, Xiaowei, Zhao, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436221/
https://www.ncbi.nlm.nih.gov/pubmed/34498711
http://dx.doi.org/10.3892/mmr.2021.12418
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author Pan, Hao
Niu, Lin
Wu, Yihao
Chen, Liuying
Zhou, Xiaowei
Zhao, Yan
author_facet Pan, Hao
Niu, Lin
Wu, Yihao
Chen, Liuying
Zhou, Xiaowei
Zhao, Yan
author_sort Pan, Hao
collection PubMed
description The irreversible loss of cardiomyocytes is mainly the result of ischemic/reperfusion (I/R) myocardial injury, leading to persistent heart dysfunction and heart failure. It has been reported that Lycium barbarum polysaccharide (LBP) has protective effects on cardiomyocytes, but the specific mechanism is still not completely understood. The present study examined the protective role of LBP in myocardial I/R injury. Rats were subjected to myocardial I/R injury and LBP treatment. Moreover, rat myocardial H9C2 cells exposed to hypoxia/reoxygenation (H/R) were used to simulate cardiac injury during myocardial I/R process and were exposed to LBP, rapamycin (an autophagy activator) or nuclear factor-erythroid factor 2-related factor 2 (Nrf2) transfection. Morphological examination, histopathological examination and echocardiography were used to determine the cardiac injury after I/R injury. Cell viability and apoptosis were determined via MTT and flow cytometry assays, respectively. The levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin T (cTnT), IL-1β, IL-6, TNF-α, malondialdehyde (MDA) and superoxidase dismutase (SOD) in rat serum, hearts and/or cells were assessed using ELISAs. The expression levels of Beclin 1, LC3II/LC3I, P62 and Nrf2 were analyzed via reverse transcription-quantitative PCR and western blotting. The results demonstrated that LBP improved heart function and repaired cardiomyocyte damage in I/R model rats, as well as reduced the production of cTnT, CK, LDH, IL-1β, IL-6 and TNF-α. The in vitro study results indicated that LBP increased cell viability, the apoptosis rate, and the levels of SOD and P62, as well as reduced the levels of LDH, CK, IL-1β, IL-6, TNF-α, MDA, Beclin 1 and LC3-II/LC3-I in H/R-injured H9C2 cells. Moreover, LBP promoted Nrf2 nuclear translocation, but decreased Nrf2 expression in the cytoplasm. Rapamycin exacerbated the aforementioned effects in H/R injured H9C2 cells, and partially reversed LBP-induced effects. Overexpressing Nrf2 counteracted I/R-induced effects and partially resisted rapamycin-induced effects. These findings demonstrated that LBP exhibited a cardiac protective effect on the ischemic myocardium of rats after reperfusion and attenuated myocardial I/R injury via autophagy inhibition-induced Nrf2 activation.
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spelling pubmed-84362212021-09-17 Lycium barbarum polysaccharide protects rats and cardiomyocytes against ischemia/reperfusion injury via Nrf2 activation through autophagy inhibition Pan, Hao Niu, Lin Wu, Yihao Chen, Liuying Zhou, Xiaowei Zhao, Yan Mol Med Rep Articles The irreversible loss of cardiomyocytes is mainly the result of ischemic/reperfusion (I/R) myocardial injury, leading to persistent heart dysfunction and heart failure. It has been reported that Lycium barbarum polysaccharide (LBP) has protective effects on cardiomyocytes, but the specific mechanism is still not completely understood. The present study examined the protective role of LBP in myocardial I/R injury. Rats were subjected to myocardial I/R injury and LBP treatment. Moreover, rat myocardial H9C2 cells exposed to hypoxia/reoxygenation (H/R) were used to simulate cardiac injury during myocardial I/R process and were exposed to LBP, rapamycin (an autophagy activator) or nuclear factor-erythroid factor 2-related factor 2 (Nrf2) transfection. Morphological examination, histopathological examination and echocardiography were used to determine the cardiac injury after I/R injury. Cell viability and apoptosis were determined via MTT and flow cytometry assays, respectively. The levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin T (cTnT), IL-1β, IL-6, TNF-α, malondialdehyde (MDA) and superoxidase dismutase (SOD) in rat serum, hearts and/or cells were assessed using ELISAs. The expression levels of Beclin 1, LC3II/LC3I, P62 and Nrf2 were analyzed via reverse transcription-quantitative PCR and western blotting. The results demonstrated that LBP improved heart function and repaired cardiomyocyte damage in I/R model rats, as well as reduced the production of cTnT, CK, LDH, IL-1β, IL-6 and TNF-α. The in vitro study results indicated that LBP increased cell viability, the apoptosis rate, and the levels of SOD and P62, as well as reduced the levels of LDH, CK, IL-1β, IL-6, TNF-α, MDA, Beclin 1 and LC3-II/LC3-I in H/R-injured H9C2 cells. Moreover, LBP promoted Nrf2 nuclear translocation, but decreased Nrf2 expression in the cytoplasm. Rapamycin exacerbated the aforementioned effects in H/R injured H9C2 cells, and partially reversed LBP-induced effects. Overexpressing Nrf2 counteracted I/R-induced effects and partially resisted rapamycin-induced effects. These findings demonstrated that LBP exhibited a cardiac protective effect on the ischemic myocardium of rats after reperfusion and attenuated myocardial I/R injury via autophagy inhibition-induced Nrf2 activation. D.A. Spandidos 2021-11 2021-09-07 /pmc/articles/PMC8436221/ /pubmed/34498711 http://dx.doi.org/10.3892/mmr.2021.12418 Text en Copyright: © Pan et al. https://creativecommons.org/licenses/by-nc-nd/4.0/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
Pan, Hao
Niu, Lin
Wu, Yihao
Chen, Liuying
Zhou, Xiaowei
Zhao, Yan
Lycium barbarum polysaccharide protects rats and cardiomyocytes against ischemia/reperfusion injury via Nrf2 activation through autophagy inhibition
title Lycium barbarum polysaccharide protects rats and cardiomyocytes against ischemia/reperfusion injury via Nrf2 activation through autophagy inhibition
title_full Lycium barbarum polysaccharide protects rats and cardiomyocytes against ischemia/reperfusion injury via Nrf2 activation through autophagy inhibition
title_fullStr Lycium barbarum polysaccharide protects rats and cardiomyocytes against ischemia/reperfusion injury via Nrf2 activation through autophagy inhibition
title_full_unstemmed Lycium barbarum polysaccharide protects rats and cardiomyocytes against ischemia/reperfusion injury via Nrf2 activation through autophagy inhibition
title_short Lycium barbarum polysaccharide protects rats and cardiomyocytes against ischemia/reperfusion injury via Nrf2 activation through autophagy inhibition
title_sort lycium barbarum polysaccharide protects rats and cardiomyocytes against ischemia/reperfusion injury via nrf2 activation through autophagy inhibition
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436221/
https://www.ncbi.nlm.nih.gov/pubmed/34498711
http://dx.doi.org/10.3892/mmr.2021.12418
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