nebulized dexmedetomidine alleviates oxidative stress in ventilator-induced lung injury via keap1-nrf2-are pathway

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.