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Hyperbaric Oxygen Upregulates Mst1 to Activate Keap1/Nrf2/HO-1 Pathway Resisting Oxidative Stress in a Rat Model of Acute Myocardial Infarction

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Abstract

This study aimed to investigate the protective effects and mechanisms of hyperbaric oxygen (HBO) preconditioning in a rat model of acute myocardial infarction (MI) established by ligation of the left anterior descending (LAD) coronary artery. Microarray, real-time PCR, and western blotting (WB) results demonstrated that the Mst1 gene was downregulated in the heart tissue of the MI rat model. HBO preconditioning significantly increased Mst1 expression in cardiac tissues of rats after MI modeling. Lentiviral infection was used to silence the Mst1 gene in rats treated with HBO to probe the effect of Mst1 on HBO cardioprotection. HBO preconditioning decreased heart infarct size and ameliorated cardiac function in MI rats, whereas Mst1 silencing reversed the effect of HBO administration, as indicated after heat infarct size determination via TTC staining, histological examination via HE staining, and measurements of cardiac function. HBO preconditioning reduced oxidative stress and inflammation in cardiac tissue of MI rat model, evidenced by alteration of malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and protein carbonyl contents, as well as production of inflammation-associated myeloperoxidase (MPO), IL-1β, and TNF-α. These findings provide a new signaling mechanism through which HBO preconditioning can protect against acute MI injury through the Mst1-mediating Keap1/Nrf2/HO-1-dependent antioxidant defense system.

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Data Availability

The data that support the findings of this study are available from the corresponding author [Di Li], upon reasonable request.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Emergency Department, Affiliated Hospital of Hebei Engineering University, Congtai District, No. 81, Congtai Road, Handan, 056008, Hebei, China

    Jianhui Liu, Yan Li, Zhigang Zhang & Di Li

  2. Department of Orthopaedics, Affiliated Hospital of Hebei Engineering University, Handan, 056008, Hebei, China

    Shubiao Wu

Authors
  1. Jianhui Liu
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  2. Yan Li
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  3. Shubiao Wu
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  4. Zhigang Zhang
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  5. Di Li
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Contributions

JL and YL designed the research plan. JL, YL, SW, ZZ, and DL performed the experiments and analyzed the data. DL wrote the manuscript.

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Correspondence to Di Li.

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All procedures were approved by the Animal Care and Use Committee of Affiliated Hospital of Hebei Engineering University.

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Liu, J., Li, Y., Wu, S. et al. Hyperbaric Oxygen Upregulates Mst1 to Activate Keap1/Nrf2/HO-1 Pathway Resisting Oxidative Stress in a Rat Model of Acute Myocardial Infarction. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01050-8

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