Anthrahydroquinone2,6disulfonate attenuates PQinduced acute lung injury through decreasing pulmonary microvascular permeability via inhibition of the PI3K/AKT/eNOS pathway.
Int J Mol Med
; 54(1)2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38874017
ABSTRACT
In paraquat (PQ)induced acute lung injury (ALI)/ acute respiratory distress syndrome, PQ disrupts endothelial cell function and vascular integrity, which leads to increased pulmonary leakage. Anthrahydroquinone2,6disulfonate (AH2QDS) is a reducing agent that attenuates the extent of renal injury and improves survival in PQintoxicated SpragueDawley (SD) rats. The present study aimed to explore the beneficial role of AH2QDS in PQinduced ALI and its related mechanisms. A PQintoxicated ALI model was established using PQ gavage in SD rats. Human pulmonary microvascular endothelial cells (HPMECs) were challenged with PQ. Superoxide dismutase, malondialdehyde, reactive oxygen species and nitric oxide (NO) fluorescence were examined to detect the level of oxidative stress in HPMECs. The levels of TNFα, IL1ß and IL6 were assessed using an ELISA. Transwell and Cell Counting Kit8 assays were performed to detect the migration and proliferation of the cells. The pathological changes in lung tissues and blood vessels were examined by haematoxylin and eosin staining. Evans blue staining was used to detect pulmonary microvascular permeability. Western blotting was performed to detect target protein levels. Immunofluorescence and immunohistochemical staining were used to detect the expression levels of target proteins in HPMECs and lung tissues. AH2QDS inhibited inflammatory responses in lung tissues and HPMECs, and promoted the proliferation and migration of HPMECs. In addition, AH2QDS reduced pulmonary microvascular permeability by upregulating the levels of vascular endothelialcadherin, zonula occludens1 and CD31, thereby attenuating pathological changes in the lungs in rats. Finally, these effects may be related to the suppression of the phosphatidylinositol3kinase (PI3K)/protein kinase B (AKT)/endothelialtype NO synthase (eNOS) signalling pathway in endothelial cells. In conclusion, AH2QDS ameliorated PQinduced ALI by improving alveolar endothelial barrier disruption via modulation of the PI3K/AKT/eNOS signalling pathway, which may be an effective candidate for the treatment of PQinduced ALI.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paraquat
/
Permeabilidade Capilar
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Transdução de Sinais
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Ratos Sprague-Dawley
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Fosfatidilinositol 3-Quinases
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Óxido Nítrico Sintase Tipo III
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Proteínas Proto-Oncogênicas c-akt
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Lesão Pulmonar Aguda
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Pulmão
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2024
Tipo de documento:
Article