Nebulized Dexmedetomidine Alleviates Oxidative Stress in Ventilator-induced Lung Injury via Keap1-Nrf2-ARE Pathway

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Zha Jun; Yu Youjia; Zhu Ji; Li Guiru; Deng Xiaolin; Xie Hong

مرکز اطلاعات علمی Scientific Information Database (SID) - Trusted Source for Research and Academic Resources

Journal Paper

Paper Information

Journal: IRANIAN JOURNAL OF ALLERGY, ASTHMA AND IMMUNOLOGY Year:2024 | Volume:23 | Issue:3 Page(s): 330-338

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Title

Nebulized Dexmedetomidine Alleviates Oxidative Stress in Ventilator-induced Lung Injury via Keap1-Nrf2-ARE Pathway

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Keywords

Inflammation; Dexmedetomidine; Nebulization; Ventilator-induced lung injury

Abstract

This study aimed to explore the underlying mechanism of nebulized dexmedetomidine (DEX) in ameliorating ventilator-induced lung injury (VILI)-induced oxidative stress in rats.
Forty 7 to 8-week-old Sprague-Dawley rats at the specific pathogen-free level were randomized into the control group, model group, nebulized dexmedetomidine (WH-YM) group, and dexmedetomidine intravenous infusion (JM-YM) group, each containing 10 rats. Except for the control group, rats in the other groups underwent mechanical ventilation (tidal volume, 40 mL/kg; respiratory rate, 70 breaths per minute; inspiratory-to-expiratory ratio, 1:2; fraction of inspired oxygen, 21%; positive end-expiratory pressure, 0 cmH2O). Nebulized DEX (6.3 µg/kg), and isodose intravenous DEX were given to rats of WH-YM and JM-YM groups prior to ventilation. Post 4-hour ventilation, rats were euthanized. Lung tissue wet-to-dry weight ratio, H&E staining for assessing diffuse alveolar damage (DAD), and expression levels of Nrf2 and Keap1 detected by qRT-PCR and Western blot were compared. Inflammatory markers TNF-α, IL-2, and IL-6, and oxidative stress indices malondialdehyde (MDA) and superoxide dismutase (SOD), were quantified in lung tissues and serum samples using commercial kits.
Rats in the WH-YM and JM-YM groups demonstrated significant ameliorations in the wet-to-dry weight ratio and DAD score, decreased Keap1, TNF-α, IL-2, and IL-6 levels in lung tissues and serum samples, but increased Nrf2 and SOD level than those of controls. These changes were more pronounced in the WH-YM group than in the JM-YM group.
DEX effectively alleviates VILI-induced oxidative stress and inflammation via the Keap1-Nrf2-ARE signaling pathway., especially in the nebulized administration.

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