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

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

doi:10.18502/ijaai.v23i3.15642

Jun Zha Department of Anesthesiology, The Second Affiliated Hospital, Soochow University, Suzhou, China
Youjia Yu Department of Anesthesiology, Suzhou Xiangcheng People’s Hospital, Suzhou, China
Ji Zhu Department of Anesthesiology, The Second Affiliated Hospital, Wannan Medical College, Wuhu, China
Guiru Li Department of Anesthesiology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China
Xiaolin Deng Department of Anesthesiology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China
Hong Xie Department of Anesthesiology, The Second Affiliated Hospital, Soochow University, Suzhou, China

DOI: https://doi.org/10.18502/ijaai.v23i3.15642

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.