Anthrahydroquinone‑2,6‑disulfonate attenuates PQ‑induced acute lung injury through decreasing pulmonary microvascular permeability via inhibition of the PI3K/AKT/eNOS pathway

Li,Nan; Yi,Yang; Chen,Jun; Huang,Yue; Peng,Jichao; Li,Zhao; Wang,Ying; Zhang,Jiadong; Xu,Chaoqun; Liu,Haoran; Li,Jinghua; Liu,Xiaoran

doi:10.3892/ijmm.2024.5387

Anthrahydroquinone‑2,6‑disulfonate attenuates PQ‑induced acute lung injury through decreasing pulmonary microvascular permeability via inhibition of the PI3K/AKT/eNOS pathway

Authors:
- Nan Li
- Yang Yi
- Jun Chen
- Yue Huang
- Jichao Peng
- Zhao Li
- Ying Wang
- Jiadong Zhang
- Chaoqun Xu
- Haoran Liu
- Jinghua Li
- Xiaoran Liu
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Affiliations: College of Emergency Trauma, Hainan Medical University, Haikou, Hainan 571199, P.R. China, Emergency Department of Danzhou People's Hospital, Danzhou, Hainan 571799, P.R. China
Published online on: June 10, 2024 https://doi.org/10.3892/ijmm.2024.5387
Article Number: 63
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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. Anthrahydroquinone‑2,6‑disulfonate (AH2QDS) is a reducing agent that attenuates the extent of renal injury and improves survival in PQ‑intoxicated Sprague‑Dawley (SD) rats. The present study aimed to explore the beneficial role of AH2QDS in PQ‑induced ALI and its related mechanisms. A PQ‑intoxicated 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 TNF‑α, IL‑1β and IL‑6 were assessed using an ELISA. Transwell and Cell Counting Kit‑8 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 endothelial‑cadherin, zonula occludens‑1 and CD31, thereby attenuating pathological changes in the lungs in rats. Finally, these effects may be related to the suppression of the phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (AKT)/endothelial‑type NO synthase (eNOS) signalling pathway in endothelial cells. In conclusion, AH2QDS ameliorated PQ‑induced 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 PQ‑induced ALI.

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