CHENG Long, ZHAO Shuchuan, CUI Jianhua, LI Jiangjiang, FENG Qian, WANG Jing
Journal of Hunan Normal University(Medical Science). 2025, 22(6): 17-22.
Objective To investigate the mechanism of dexmedetomidine regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1) signaling pathway on oxidative stress and inflammatory response in lipopolysaccharide-induced acute lung injury (ALI). Methods Mice were randomly divided into a blank control group (Control group), ALI mouse model group (ALI group), dexmedetomidine intervention group (DEX group), and dexmedetomidine combined with Nrf2 inhibitor ML385 group (DEX+ML385 group). Calculate the wet/dry weight ratio of lung tissue, detect pathological changes in lung tissue using HE staining, detect oxidative stress indicators in lung tissue and levels of inflammatory factors in alveolar lavage fluid, and detect the expression of Nrf2 and HO-1 proteins in lung tissue using Western blotting. Results Compared with the control group, mice in the ALI group showed significantly higher lung tissue wet/dry weight ratio (W/D), lung injury pathological score, counts of total cells, neutrophils and macrophages in bronchoalveolar lavage fluid (BALF), levels of tumor necrosis factor-α (TNF-α), interleukin (IL) -6, IL-1β and IL-18, as well as malondialdehyde (MDA) content and myeloperoxidase (MPO) activity in lung tissue. In contrast, glutathione peroxidase (GSH-Px) content, superoxide dismutase (SOD) activity, and protein expressions of nuclear factor erythroid 2-related factor 2(Nrf2) and heme oxygenase-1(HO-1) in lung tissue were markedly lower in the ALI group. Compared with the ALI group, the DEX group showed significantly decreased lung tissue W/D value, lung injury histopathological score, total cell count, neutrophil count, macrophage count, TNF-α, IL-6, IL-1β, IL-18 levels in BALF, lung tissue MDA content and MPO activity. Moreover, the DEX group exhibited significantly increased lung tissue GSH-Px content, SOD activity, Nrf2, and HO-1 protein expression. However, compared with the DEX group, the DEX AL385 group showed significantly increased lung tissue W/D value, lung injury histopathological score, total cell count, neutrophil count, macrophage count, TNF-α, IL-6, IL-1β, IL-18 levels in BALF, lung tissue MDA content and MPO activity. Additionally, the DEX AL385 group exhibited significantly decreased lung tissue GSH-Px content, SOD activity, Nrf2, and HO-1 protein expression (P<0.05). Conclusion Dexmetomidine can improve the antioxidant capacity and inhibit inflammatory response in lipopolysaccharide-induced acute lung injury mice, thereby exerting a protective effect on lung tissue. Its mechanism of action may be related to the activation of the Nrf2/HO-1 signaling pathway.