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Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation

BACKGROUND: Ventilator-induced lung injury (VILI) is a common complication of mechanical ventilation under general anesthesia. Regular aerobic exercise before surgery improves postoperative recovery and reduces postoperative pulmonary complications, but the mechanism driving this protective effect i...

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Autores principales: YAN, JIE, GU, CHANGPING, LIU, GE, ZHANG, YAQIANG, YANG, LI, ZHAO, TAO, CAO, CUICUI, ZHAO, LIANG, WU, GUANGHAN, WANG, YUELAN
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487353/
https://www.ncbi.nlm.nih.gov/pubmed/37144632
http://dx.doi.org/10.1249/MSS.0000000000003203
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author YAN, JIE
GU, CHANGPING
LIU, GE
ZHANG, YAQIANG
YANG, LI
ZHAO, TAO
CAO, CUICUI
ZHAO, LIANG
WU, GUANGHAN
WANG, YUELAN
author_facet YAN, JIE
GU, CHANGPING
LIU, GE
ZHANG, YAQIANG
YANG, LI
ZHAO, TAO
CAO, CUICUI
ZHAO, LIANG
WU, GUANGHAN
WANG, YUELAN
author_sort YAN, JIE
collection PubMed
description BACKGROUND: Ventilator-induced lung injury (VILI) is a common complication of mechanical ventilation under general anesthesia. Regular aerobic exercise before surgery improves postoperative recovery and reduces postoperative pulmonary complications, but the mechanism driving this protective effect is unclear. METHODS: To determine how aerobic exercise prevents VILI, we investigated the effects of exercise and mechanical ventilation on the lungs of male mice and the effects of AMPK stimulation (simulating exercise) and cyclic stretching on human lung microvascular endothelial cells (HLMVEC). Sirtuin 1 (Sirt1) knockdown male mice were generated to explore the regulating mechanisms of sirt1 on mitochondrial function in male mice after mechanical ventilation was explored. Western blot, flow cytometry, live cell imaging, and mitochondrial function evaluations were used to determine the protective effects of aerobic exercise in preventing mitochondrial damage in VILI. RESULTS: Mitochondrial function and cell junctions were destroyed by mechanical ventilation in male mice or cyclic stretching in HLMVEC, a model of VILI. However, mitochondrial function and cell junction dysfunction were improved by exercise before mechanical ventilation (male mice) or treatment with AMPK before cyclic stretching (HLMVEC). p66shc, a marker of oxidative stress, was increased, and PINK1, a marker of mitochondrial autophagy, was decreased by mechanical ventilation or cyclic stretching. Sirt1 knockdown increased p66shc and decreased PINK1. Increased sirt1 expression was observed in the exercise and exercise + ventilation groups, suggesting that sirt1 inhibits mitochondrial damage in VILI. CONCLUSIONS: Mechanical ventilation induces mitochondrial damage in lung cells and leads to VILI. Regular aerobic exercise before ventilation may prevent VILI by improving mitochondrial function.
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spelling pubmed-104873532023-09-09 Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation YAN, JIE GU, CHANGPING LIU, GE ZHANG, YAQIANG YANG, LI ZHAO, TAO CAO, CUICUI ZHAO, LIANG WU, GUANGHAN WANG, YUELAN Med Sci Sports Exerc Basic Sciences BACKGROUND: Ventilator-induced lung injury (VILI) is a common complication of mechanical ventilation under general anesthesia. Regular aerobic exercise before surgery improves postoperative recovery and reduces postoperative pulmonary complications, but the mechanism driving this protective effect is unclear. METHODS: To determine how aerobic exercise prevents VILI, we investigated the effects of exercise and mechanical ventilation on the lungs of male mice and the effects of AMPK stimulation (simulating exercise) and cyclic stretching on human lung microvascular endothelial cells (HLMVEC). Sirtuin 1 (Sirt1) knockdown male mice were generated to explore the regulating mechanisms of sirt1 on mitochondrial function in male mice after mechanical ventilation was explored. Western blot, flow cytometry, live cell imaging, and mitochondrial function evaluations were used to determine the protective effects of aerobic exercise in preventing mitochondrial damage in VILI. RESULTS: Mitochondrial function and cell junctions were destroyed by mechanical ventilation in male mice or cyclic stretching in HLMVEC, a model of VILI. However, mitochondrial function and cell junction dysfunction were improved by exercise before mechanical ventilation (male mice) or treatment with AMPK before cyclic stretching (HLMVEC). p66shc, a marker of oxidative stress, was increased, and PINK1, a marker of mitochondrial autophagy, was decreased by mechanical ventilation or cyclic stretching. Sirt1 knockdown increased p66shc and decreased PINK1. Increased sirt1 expression was observed in the exercise and exercise + ventilation groups, suggesting that sirt1 inhibits mitochondrial damage in VILI. CONCLUSIONS: Mechanical ventilation induces mitochondrial damage in lung cells and leads to VILI. Regular aerobic exercise before ventilation may prevent VILI by improving mitochondrial function. Lippincott Williams & Wilkins 2023-10 2023-05-05 /pmc/articles/PMC10487353/ /pubmed/37144632 http://dx.doi.org/10.1249/MSS.0000000000003203 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Basic Sciences
YAN, JIE
GU, CHANGPING
LIU, GE
ZHANG, YAQIANG
YANG, LI
ZHAO, TAO
CAO, CUICUI
ZHAO, LIANG
WU, GUANGHAN
WANG, YUELAN
Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation
title Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation
title_full Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation
title_fullStr Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation
title_full_unstemmed Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation
title_short Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation
title_sort aerobic exercise in male mice prevents ventilator-induced lung injury by inhibiting mitochondrial damage from sirt1 dysregulation
topic Basic Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487353/
https://www.ncbi.nlm.nih.gov/pubmed/37144632
http://dx.doi.org/10.1249/MSS.0000000000003203
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