A novel tree shrew model of lipopolysaccharide-induced acute respiratory distress syndrome

Abstract

Introduction: Acute respiratory distress syndrome (ARDS) is a leading cause of respiratory failure, with substantial attributable morbidity and mortality. The small animal models that are currently used for ARDS do not fully manifest all of the pathological hallmarks of human patients, which hampers both the studies of disease mechanism and drug development.

Objectives: To examine whether the phenotypic changes of primate-like tree shrews in response to a one-hit lipopolysaccharides (LPS) injury resemble human ARDS features.

Methods: LPS was administered to tree shrews through intratracheal instillation; then, the animals underwent CT or PET/CT imaging to examine the changes in the structure and function of the whole lung. The lung histology was analyzed by H&E staining and immunohistochemical staining of inflammatory cells.

Results: Results demonstrated that tree shrews exhibited an average survival time of 3-5 days after LPS insult, as well as an obvious symptom of dyspnea before death. The ratios of PaO₂ to FiO₂ (P/F ratio) were close to those of moderate ARDS in humans. CT imaging showed that the scope of the lung injury in tree shrews after LPS treatment were extensive. PET/CT imaging with ¹⁸F-FDG displayed an obvious inflammatory infiltration. Histological analysis detected the formation of a hyaline membrane, which is usually present in human ARDS.

Conclusion: This study established a lung injury model with a primate-like small animal model and confirmed that they have similar features to human ARDS, which might provide a valuable tool for translational research.

Keywords: Acute respiratory distress syndrome; Lipopolysaccharide; One-hit; Tree shrew.