Changli Wang, Yan Meng, Yuanyuan Wang, Zhengyu Jiang, Mengda Xu, Lulong Bo, Xiaoming Deng
Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China (mainland)
Med Sci Monit 2018; 24: ANS4455-4464
Available online: 2018-06-28
Ouabain, an inhibitor of Na+/K+-ATPase, is a type of endogenous hormone synthesized in the adrenal cortex and hypothalamus. Previous studies found that ouabain potently inhibited inflammatory reactions and regulated immunological processes. Our present study aimed to investigate the therapeutic role of ouabain on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.
MATERIAL AND METHODS: Ouabain (0.1 mg/kg) or vehicles were intraperitoneally injected into male C57BL/6J mice once a day for 3 consecutive days. One hour after the last injection of ouabain, LPS (5 mg/kg) was administrated through intranasal instillation to induce ALI. 6 hours and 24 hours later, bronchoalveolar lavage ﬂuid (BALF) and lung tissues were harvested to detect the protective effects of ouabain, including protein concentration, inflammation cell counts, lung wet-to-dry ratio, and lung damage.
RESULTS: The results showed that ouabain attenuated LPS-induced ALI in mice, which was indicated by alleviated pathological changes, downregulated TNF-α, IL-1β, and IL-6 production, inhibited neutrophils infiltration and macrophages, and ameliorated pulmonary edema and permeability. Further results found the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were suppressed by ouabain in LPS-induced ALI.
CONCLUSIONS: These results suggest that ouabain negatively modulates the severity of LPS-induced ALI.
Keywords: acute lung injury, Lipopolysaccharides, Mitogen-Activated Protein Kinase Kinases, NF-kappa B