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The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest
Deep hypothermic circulatory arrest (DHCA) can cause acute lung injury (ALI), and its pathogenesis mimics ischaemia/reperfusion (I/R) injury. Autophagy is also involved in lung I/R injury. The present study aimed to elucidate whether DHCA induces natural autophagy activation and its role in DHCA‐med...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831962/ https://www.ncbi.nlm.nih.gov/pubmed/35014165 http://dx.doi.org/10.1111/jcmm.17165 |
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author | Kong, Minjian Wei, Dongdong Li, Xuebiao Zhu, Xian Hong, Ze Ni, Ming Wang, Yifan Dong, Aiqiang |
author_facet | Kong, Minjian Wei, Dongdong Li, Xuebiao Zhu, Xian Hong, Ze Ni, Ming Wang, Yifan Dong, Aiqiang |
author_sort | Kong, Minjian |
collection | PubMed |
description | Deep hypothermic circulatory arrest (DHCA) can cause acute lung injury (ALI), and its pathogenesis mimics ischaemia/reperfusion (I/R) injury. Autophagy is also involved in lung I/R injury. The present study aimed to elucidate whether DHCA induces natural autophagy activation and its role in DHCA‐mediated lung injury. Here, rats were randomly assigned to the Sham or DHCA group. The sham group (n = 5) only received anaesthesia and air intubation. DHCA group rats underwent cardiopulmonary bypass (CPB) followed by the DHCA procedure. The rats were then sacrificed at 3, 6 and 24 h after the DHCA procedure (n = 5) to measure lung injury and autophagy activity. Chloroquine (CQ) was delivered to evaluate autophagic flux. DHCA caused lung injury, which was prominent 3–6 h after DHCA, as confirmed by histological examination and inflammatory cytokine quantification. Lung injury subsided at 24 h. Autophagy was suppressed 3 h but was exaggerated at 6 h. At both time points, autophagic flux appeared uninterrupted. To further assess the role of autophagy in DHCA‐mediated lung injury, the autophagy inducer rapamycin and its inhibitor 3‐methyladenine (3‐MA) were applied, and lung injury was reassessed. When rapamycin was administered at an early time point, lung injury worsened, whereas administration of 3‐MA at a late time point ameliorated lung injury, indicating that autophagy contributed to lung injury after DHCA. Our study presents a time course of lung injury following DHCA. Autophagy showed adaptive yet protective suppression 3 h after DHCA, as induction of autophagy caused worsening of lung tissue. In contrast, autophagy was exaggerated 6 h after DHCA, and autophagy inhibition attenuated DHCA‐mediated lung injury. |
format | Online Article Text |
id | pubmed-8831962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88319622022-02-14 The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest Kong, Minjian Wei, Dongdong Li, Xuebiao Zhu, Xian Hong, Ze Ni, Ming Wang, Yifan Dong, Aiqiang J Cell Mol Med Original Articles Deep hypothermic circulatory arrest (DHCA) can cause acute lung injury (ALI), and its pathogenesis mimics ischaemia/reperfusion (I/R) injury. Autophagy is also involved in lung I/R injury. The present study aimed to elucidate whether DHCA induces natural autophagy activation and its role in DHCA‐mediated lung injury. Here, rats were randomly assigned to the Sham or DHCA group. The sham group (n = 5) only received anaesthesia and air intubation. DHCA group rats underwent cardiopulmonary bypass (CPB) followed by the DHCA procedure. The rats were then sacrificed at 3, 6 and 24 h after the DHCA procedure (n = 5) to measure lung injury and autophagy activity. Chloroquine (CQ) was delivered to evaluate autophagic flux. DHCA caused lung injury, which was prominent 3–6 h after DHCA, as confirmed by histological examination and inflammatory cytokine quantification. Lung injury subsided at 24 h. Autophagy was suppressed 3 h but was exaggerated at 6 h. At both time points, autophagic flux appeared uninterrupted. To further assess the role of autophagy in DHCA‐mediated lung injury, the autophagy inducer rapamycin and its inhibitor 3‐methyladenine (3‐MA) were applied, and lung injury was reassessed. When rapamycin was administered at an early time point, lung injury worsened, whereas administration of 3‐MA at a late time point ameliorated lung injury, indicating that autophagy contributed to lung injury after DHCA. Our study presents a time course of lung injury following DHCA. Autophagy showed adaptive yet protective suppression 3 h after DHCA, as induction of autophagy caused worsening of lung tissue. In contrast, autophagy was exaggerated 6 h after DHCA, and autophagy inhibition attenuated DHCA‐mediated lung injury. John Wiley and Sons Inc. 2022-01-11 2022-02 /pmc/articles/PMC8831962/ /pubmed/35014165 http://dx.doi.org/10.1111/jcmm.17165 Text en © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Kong, Minjian Wei, Dongdong Li, Xuebiao Zhu, Xian Hong, Ze Ni, Ming Wang, Yifan Dong, Aiqiang The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest |
title | The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest |
title_full | The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest |
title_fullStr | The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest |
title_full_unstemmed | The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest |
title_short | The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest |
title_sort | dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831962/ https://www.ncbi.nlm.nih.gov/pubmed/35014165 http://dx.doi.org/10.1111/jcmm.17165 |
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