Abstract

Ventilator-induced lung injury (VILI) is an important critical care complication. Nuclear factor-κB (NF-κB) activation, a critical signaling event in the inflammatory response, has been implicated in the tracking of the lung injury. The present study aimed to determine the effect of simultaneous pretreatment with enteral aspirin and omega-3 fatty acid on lung injury in a murine VILI model. We compared the lung inflammation after the sequential administration of lipopolysaccharides and mechanical ventilation between the pretreated simultaneous enteral aspirin and omega-3 fatty acid group and the non-pretreatment group, by quantifying NF-κB activation using an in vivo imaging system to detect bioluminescence signals. The pretreated group with enteral aspirin and omega-3 fatty acid exhibited a smaller elevation of bioluminescence signals than the non-pretreated group (p = 0.039). Compared to the non-pretreated group, the pretreatment group with simultaneous enteral aspirin and omega-3 fatty acid showed reduced expression of the pro-inflammatory cytokine, tumor necrosis factor-α, in bronchoalveolar lavage fluid (p = 0.038). Histopathological lung injury scores were also lower in the pretreatment groups compared to the only injury group. Simultaneous pretreatment with enteral administration of aspirin and omega-3 fatty acid could be a prevention method for VILI in patients with impending mechanical ventilation therapy.

Highlights

  • Since the introduction of mechanical ventilation (MV) in the 1960s, it has been widely adopted in clinical practices, and inevitably ventilator-induced lung injury (VILI) has become an important topic for study in critical care

  • We compared the changes in Nuclear factor-κB (NF-κB) signal activity 4 h after the lung injury among injury only, resolvin D1 (RvD1) pretreatment, and pretreated simultaneous enteral aspirin and omega-3 fatty acid groups using an in vivo imaging system to detect the bioluminescence signal

  • Mice pretreated with aspirin and omega-3 fatty acid showed a significantly minimal change of signal activities (p/s/cm2 /sr) 4 h after MV injury than those in the injury only group (7.5 × 104 ± 3.1 × vs. 4.7 × ± 1.4 × 105, p = 0.039)

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Summary

Introduction

Since the introduction of mechanical ventilation (MV) in the 1960s, it has been widely adopted in clinical practices, and inevitably ventilator-induced lung injury (VILI) has become an important topic for study in critical care. Several researchers have shown that blockades to the NF-κB pathway can attenuate inflammatory responses to MV and decrease the incidence and severity of lung injury [3,4]. Patients at risk of developing acute lung injury (ALI) and with established ALI had low levels of omega-3 compared to normal Aspirin represents a positive effect to elicit reduction in the ALI by attenuating inflammatory mediators and increasing restitution of pulmonary barrier function and resolution of injury [9]. We performed this study to explore the ability of pretreated simultaneous enteral aspirin and omega-3 fatty acid to attenuate lung inflammation in the murine VILI model

Animals and Study Design
Ventilator-Induced Lung Injury Model
Anti-Inflammatory Compounds
In Vivo Imaging to Evaluate NF-κB-Luciferase Assay
Statistical Analyses
Setting of VILI Model
In Vivo Imaging of NF-κB Activation
Histopathological Examination
Discussion
Conclusions

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