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Hydrogen Sulfide Ameliorates Lung Ischemia-Reperfusion Injury Through SIRT1 Signaling Pathway in Type 2 Diabetic Rats

Lung ischemia-reperfusion (IR) injury remains a significant factor for the early mortality of lung transplantations. Diabetes mellitus (DM) is an independent risk factor for 5-year mortality following lung transplantation. Our previous study showed that DM aggravated lung IR injury and that oxidativ...

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Autores principales: Jiang, Tao, Yang, Weiwei, Zhang, Hongli, Song, Zhiqiang, Liu, Tianhua, Lv, Xiangqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338566/
https://www.ncbi.nlm.nih.gov/pubmed/32695008
http://dx.doi.org/10.3389/fphys.2020.00596
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author Jiang, Tao
Yang, Weiwei
Zhang, Hongli
Song, Zhiqiang
Liu, Tianhua
Lv, Xiangqi
author_facet Jiang, Tao
Yang, Weiwei
Zhang, Hongli
Song, Zhiqiang
Liu, Tianhua
Lv, Xiangqi
author_sort Jiang, Tao
collection PubMed
description Lung ischemia-reperfusion (IR) injury remains a significant factor for the early mortality of lung transplantations. Diabetes mellitus (DM) is an independent risk factor for 5-year mortality following lung transplantation. Our previous study showed that DM aggravated lung IR injury and that oxidative stress played a key role in this process. Previously, we demonstrated that hydrogen sulfide (H(2)S) protected against diabetic lung IR injury by suppressing oxidative damage. This study aimed to examine the mechanism by which H(2)S affects diabetic lung IR injury. High-fat-diet-fed streptozotocin-induced type 2 diabetic rats were exposed to GYY4137, a slow-releasing H(2)S donor with or without administration of EX527 (a SIRT1 inhibitor), and then subjected to a surgical model of IR injury of the lung. Lung function, oxidative stress, cell apoptosis, and inflammation were assessed. We found that impairment of lung SIRT1 signaling under type 2 diabetic conditions was further exacerbated by IR injury. GYY4137 treatment markedly activated SIRT1 signaling and ameliorated lung IR injury in type 2 DM animals by improving lung functional recovery, diminishing oxidative damage, reducing inflammation, and suppressing cell apoptosis. However, these effects were largely compromised by EX527. Additionally, treatment with GYY4137 significantly activated the Nrf2/HO-1 antioxidant signaling pathway and increased eNOS phosphorylation. However, these effects were largely abolished by EX527. Together, our results indicate that GYY4137 treatment effectively attenuated lung IR injury under type 2 diabetic conditions via activation of lung SIRT1 signaling. SIRT1 activation upregulated Nrf2/HO-1 and activated the eNOS-mediated antioxidant signaling pathway, thus reducing cell apoptosis and inflammation and eventually preserving lung function.
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spelling pubmed-73385662020-07-20 Hydrogen Sulfide Ameliorates Lung Ischemia-Reperfusion Injury Through SIRT1 Signaling Pathway in Type 2 Diabetic Rats Jiang, Tao Yang, Weiwei Zhang, Hongli Song, Zhiqiang Liu, Tianhua Lv, Xiangqi Front Physiol Physiology Lung ischemia-reperfusion (IR) injury remains a significant factor for the early mortality of lung transplantations. Diabetes mellitus (DM) is an independent risk factor for 5-year mortality following lung transplantation. Our previous study showed that DM aggravated lung IR injury and that oxidative stress played a key role in this process. Previously, we demonstrated that hydrogen sulfide (H(2)S) protected against diabetic lung IR injury by suppressing oxidative damage. This study aimed to examine the mechanism by which H(2)S affects diabetic lung IR injury. High-fat-diet-fed streptozotocin-induced type 2 diabetic rats were exposed to GYY4137, a slow-releasing H(2)S donor with or without administration of EX527 (a SIRT1 inhibitor), and then subjected to a surgical model of IR injury of the lung. Lung function, oxidative stress, cell apoptosis, and inflammation were assessed. We found that impairment of lung SIRT1 signaling under type 2 diabetic conditions was further exacerbated by IR injury. GYY4137 treatment markedly activated SIRT1 signaling and ameliorated lung IR injury in type 2 DM animals by improving lung functional recovery, diminishing oxidative damage, reducing inflammation, and suppressing cell apoptosis. However, these effects were largely compromised by EX527. Additionally, treatment with GYY4137 significantly activated the Nrf2/HO-1 antioxidant signaling pathway and increased eNOS phosphorylation. However, these effects were largely abolished by EX527. Together, our results indicate that GYY4137 treatment effectively attenuated lung IR injury under type 2 diabetic conditions via activation of lung SIRT1 signaling. SIRT1 activation upregulated Nrf2/HO-1 and activated the eNOS-mediated antioxidant signaling pathway, thus reducing cell apoptosis and inflammation and eventually preserving lung function. Frontiers Media S.A. 2020-06-30 /pmc/articles/PMC7338566/ /pubmed/32695008 http://dx.doi.org/10.3389/fphys.2020.00596 Text en Copyright © 2020 Jiang, Yang, Zhang, Song, Liu and Lv. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Jiang, Tao
Yang, Weiwei
Zhang, Hongli
Song, Zhiqiang
Liu, Tianhua
Lv, Xiangqi
Hydrogen Sulfide Ameliorates Lung Ischemia-Reperfusion Injury Through SIRT1 Signaling Pathway in Type 2 Diabetic Rats
title Hydrogen Sulfide Ameliorates Lung Ischemia-Reperfusion Injury Through SIRT1 Signaling Pathway in Type 2 Diabetic Rats
title_full Hydrogen Sulfide Ameliorates Lung Ischemia-Reperfusion Injury Through SIRT1 Signaling Pathway in Type 2 Diabetic Rats
title_fullStr Hydrogen Sulfide Ameliorates Lung Ischemia-Reperfusion Injury Through SIRT1 Signaling Pathway in Type 2 Diabetic Rats
title_full_unstemmed Hydrogen Sulfide Ameliorates Lung Ischemia-Reperfusion Injury Through SIRT1 Signaling Pathway in Type 2 Diabetic Rats
title_short Hydrogen Sulfide Ameliorates Lung Ischemia-Reperfusion Injury Through SIRT1 Signaling Pathway in Type 2 Diabetic Rats
title_sort hydrogen sulfide ameliorates lung ischemia-reperfusion injury through sirt1 signaling pathway in type 2 diabetic rats
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338566/
https://www.ncbi.nlm.nih.gov/pubmed/32695008
http://dx.doi.org/10.3389/fphys.2020.00596
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