Establish of a mouse model of COPD that meets clinical criteria by LPS+cigarette smoke exposure for 12 weeks

Abstract

Objective To investigate whether the induction of lipopolysaccharide (LPS) combined with cigarette smoke (CS) for 12 weeks can successfully construct a mouse model of chronic obstructive pulmonary disease (COPD) that meets clinical criteria. Methods Thirty male C57BL/6 mice (8 weeks old, 20~25 g) were subjected and randomly divided into model (n=15) and control groups (n=15).A combined induction of LPS+CS was used for modeling, and LPS (2 mg/kg) was administered intratracheally only on days 1 and 14, while CS exposure (2 times/d, 10 cigarettes, 60 min/time) was conducted on the other days during the induction for 12 weeks.The same batch of mice were given no intervention and served as the control group.Changes in lung histopathology (HE and Masson staining), inflammatory factor levels (IFN-γ, IL-12, TNF-α and IL-6) and lung function (FEV0.1/FVC%) were compared between the 2 groups of mice after modeling. Results When compared with the control group, LPS+CS induction resulted in obvious fibrosis of bronchial smooth muscle layer, alveolar diaphragm dissection, alveolar fusion, and significantly increased mean alveolar intercept (P < 0.001), obviously decreased mean alveolar number (P < 0.001), notably elevated systemic and pulmonary pro-inflammatory factors IFN-γ, IL-12, TNF-α and IL-6 levels, and reduced FEV0.1/FVC% value (P < 0.001).Mean alveolar intercept and FEV0.1/FVC% were extremely significantly negatively correlated (r=-0.922 6, P < 0.001), while mean alveolar number and FEV0.1/FVC% had extremely significant positive correlation (r=0.933 0, P < 0.001). Conclusion A mouse model of COPD that meets clinical criteria can be established successfully with LPS+CS induction for 12 weeks.

Keywords

• cigarette smoke
• lipopolysaccharide
• chronic obstructive pulmonary disease
• clinical criteria