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The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms
BACKGROUND: The aim of the present study was to investigate the protective effects of protease inhibitor MG-132 on sepsis-induced acute lung injury rats. MATERIAL/METHODS: Sprague Dawley rats were employed to induce sepsis by cecal ligation and puncture (CLP) method. Rats were divided into 4 groups:...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688517/ https://www.ncbi.nlm.nih.gov/pubmed/31366881 http://dx.doi.org/10.12659/MSM.915743 |
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author | Wu, Bingbing Miao, Xiaoli Ye, Jilu Pu, Xuehua |
author_facet | Wu, Bingbing Miao, Xiaoli Ye, Jilu Pu, Xuehua |
author_sort | Wu, Bingbing |
collection | PubMed |
description | BACKGROUND: The aim of the present study was to investigate the protective effects of protease inhibitor MG-132 on sepsis-induced acute lung injury rats. MATERIAL/METHODS: Sprague Dawley rats were employed to induce sepsis by cecal ligation and puncture (CLP) method. Rats were divided into 4 groups: control, sham, model (CLP), and MG-132. Histopathology observation was detected by hematoxylin and eosin staining. The ratio of wet lung to dry lung (W/D) was calculated. In addition, the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Also, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were evaluated. Western blotting was performed to measure the expression of hypoxia-inducible factor-1 α (HIF-1α). In order to assess the role of HIF-1α, YC-1, the inhibitor of HIF-1α, was used to treat the rats. The expression of phosphor-mTOR (p-mTOR), p-4EBP1, and p-EIF4E were evaluated by western blotting. RESULTS: Obvious pathological injury and increasing ratio of W/D in the model group were observed. Both pathological injury and W/D were improved in the MG-132 group, and the greatest improvement could be seen in the YC-1+MG-132 group. Furthermore, the MDA levels in the MG-132 group was decreased, accompanied by an increase in SOD levels. The level of HIF-1α was increased in the model group while a decreased was detected in the MG-132 group. The levels of inflammatory factors were high in the model group, whereas the opposite result was found in the MG-132 group, and the lowest in were in the YC-1+MG-132 group. Furthermore, the expression levels of p-mTOR, p-4EBP1, and p-EIF4E proteins were downregulated in the MG-132 group compared to the model group, and the lowest was in the YC-1+MG-132 group. CONCLUSIONS: Our study suggested that MG-132 was able to protect against acute lung injury via inhibition of HIF-1α mediated mTOR/4EBP1/EIF4E pathway. |
format | Online Article Text |
id | pubmed-6688517 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66885172019-08-28 The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms Wu, Bingbing Miao, Xiaoli Ye, Jilu Pu, Xuehua Med Sci Monit Animal Study BACKGROUND: The aim of the present study was to investigate the protective effects of protease inhibitor MG-132 on sepsis-induced acute lung injury rats. MATERIAL/METHODS: Sprague Dawley rats were employed to induce sepsis by cecal ligation and puncture (CLP) method. Rats were divided into 4 groups: control, sham, model (CLP), and MG-132. Histopathology observation was detected by hematoxylin and eosin staining. The ratio of wet lung to dry lung (W/D) was calculated. In addition, the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Also, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were evaluated. Western blotting was performed to measure the expression of hypoxia-inducible factor-1 α (HIF-1α). In order to assess the role of HIF-1α, YC-1, the inhibitor of HIF-1α, was used to treat the rats. The expression of phosphor-mTOR (p-mTOR), p-4EBP1, and p-EIF4E were evaluated by western blotting. RESULTS: Obvious pathological injury and increasing ratio of W/D in the model group were observed. Both pathological injury and W/D were improved in the MG-132 group, and the greatest improvement could be seen in the YC-1+MG-132 group. Furthermore, the MDA levels in the MG-132 group was decreased, accompanied by an increase in SOD levels. The level of HIF-1α was increased in the model group while a decreased was detected in the MG-132 group. The levels of inflammatory factors were high in the model group, whereas the opposite result was found in the MG-132 group, and the lowest in were in the YC-1+MG-132 group. Furthermore, the expression levels of p-mTOR, p-4EBP1, and p-EIF4E proteins were downregulated in the MG-132 group compared to the model group, and the lowest was in the YC-1+MG-132 group. CONCLUSIONS: Our study suggested that MG-132 was able to protect against acute lung injury via inhibition of HIF-1α mediated mTOR/4EBP1/EIF4E pathway. International Scientific Literature, Inc. 2019-08-01 /pmc/articles/PMC6688517/ /pubmed/31366881 http://dx.doi.org/10.12659/MSM.915743 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) ) |
spellingShingle | Animal Study Wu, Bingbing Miao, Xiaoli Ye, Jilu Pu, Xuehua The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms |
title | The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms |
title_full | The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms |
title_fullStr | The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms |
title_full_unstemmed | The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms |
title_short | The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms |
title_sort | protective effects of protease inhibitor mg-132 on sepsis-induced acute lung rats and its possible mechanisms |
topic | Animal Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688517/ https://www.ncbi.nlm.nih.gov/pubmed/31366881 http://dx.doi.org/10.12659/MSM.915743 |
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