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Updated: Feb 8, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Ouabain Protects Mice Against Lipopolysaccharide-Induced Acute Lung Injury
Changli Wang1, Yan Meng1, Yuanyuan Wang1,2
1Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China (mainland).
Abstract:
BACKGROUND 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.
Insights
Ouabain, an inhibitor of Na+/K+-ATPase, effectively reduced the severity of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. This cardiac glycoside attenuated inflammation and protected lung tissues by inhibiting key signaling pathways.
Area of Science:
- Cardiovascular Pharmacology
- Pulmonary Medicine
- Immunology
Background:
- Ouabain, a Na+/K+-ATPase inhibitor and endogenous hormone, is known to modulate inflammatory and immunological responses.
- Previous research indicates ouabain's potential in regulating inflammatory reactions.
- This study investigates ouabain's therapeutic efficacy in a mouse model of acute lung injury.
Purpose of the Study:
- To evaluate the protective role of ouabain against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.
- To determine the impact of ouabain on inflammatory markers and lung tissue damage in ALI.
- To explore the underlying molecular mechanisms, including NF-κB and MAPK pathways.
Main Methods:
- Male C57BL/6J mice were administered ouabain (0.1 mg/kg) or vehicle daily for three days.
- Acute lung injury was induced via intranasal lipopolysaccharide (LPS) instillation one hour after the final ouabain dose.
- Bronchoalveolar lavage fluid and lung tissues were collected at 6 and 24 hours post-LPS for analysis.
Main Results:
- Ouabain significantly attenuated LPS-induced ALI, reducing pathological lung changes and pulmonary edema.
- Treatment with ouabain downregulated pro-inflammatory cytokines TNF-α, IL-1β, and IL-6.
- Ouabain inhibited neutrophil and macrophage infiltration and suppressed NF-κB and MAPK signaling pathway activation.
Conclusions:
- Ouabain demonstrates a significant therapeutic effect in mitigating the severity of LPS-induced acute lung injury.
- The anti-inflammatory and protective effects of ouabain are mediated through the suppression of key inflammatory signaling pathways.
- Ouabain represents a potential therapeutic agent for managing acute lung injury.
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