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Resveratrol Attenuates Intermittent Hypoxia-Induced Lung Injury by Activating the Nrf2/ARE Pathway

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Abstract

Purpose

Obstructive sleep apnea (OSA) is associated with lung injury. As a novel pathophysiological hallmark of OSA, chronic intermittent hypoxia (CIH) enhances apoptosis. The present study aims to evaluate the effect of resveratrol (Res) on CIH-induced lung apoptosis and inflammation in a rat model of CIH.

Methods

Rats were randomly allocated to normoxia (control), CIH, and CIH + Res groups (n = 10 in each group). The CIH exposure duration was 12 weeks. Rats in the CIH + Res group were additionally administered Res (50 mg kg–1 d–1). Inflammatory cytokine levels were detected by enzyme-linked immunosorbent assays (ELISAs). A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was conducted to evaluate the apoptosis rate. Bax, cleaved caspase-3, Nrf2 and HO-1 protein levels were detected by western blotting.

Results

The IL-6 and TNF-α levels in the serum and alveolar lavage fluid in the CIH group were markedly higher than those in the control group. The percentage of apoptotic cells in the CIH group was higher than that in the control group. Bax and cleaved caspase-3 protein levels were increased in the CIH group compared with those in the control group. Nrf2 and HO-1 protein levels were decreased in the CIH group compared with those in the control group (p < 0.05). Compared with the CIH group, rats in the CIH + Res group had lower percentages of apoptotic cells, lower IL-6, TNF-α, Bax and cleaved caspase-3 protein levels, and higher Nrf2 and HO-1 protein levels (p < 0.05).

Conclusion

Res attenuates CIH-related inflammatory reactions and apoptosis in lung tissue by activating the Nrf2/ARE pathway.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81870074) and the Medical Elite Cultivation Program of Fujian in China (No. 2017-ZQN-43).

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Author notes

  1. Ningfang Lian and Shuyi Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China

    Ningfang Lian, Shuyi Zhang, Jiefeng Huang, Ting Lin & Qichang Lin

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  1. Ningfang Lian
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Contributions

Conception and design: NL, SZ, and QL. Collection and assembly of data: NL, SZ, and JH. Data analysis and interpretation: NL and SZ. Manuscript writing: all authors. Manuscript revision: NL and SZ. Final approval of the manuscript: all authors.

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Correspondence to Qichang Lin.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving animals were approved by the appropriate ethics committee and were performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments.

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Lian, N., Zhang, S., Huang, J. et al. Resveratrol Attenuates Intermittent Hypoxia-Induced Lung Injury by Activating the Nrf2/ARE Pathway. Lung 198, 323–331 (2020). https://doi.org/10.1007/s00408-020-00321-w

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  • DOI: https://doi.org/10.1007/s00408-020-00321-w

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