Comparison and evaluation of two different methods to establish the cigarette smoke exposure mouse model of COPD

Abstract

Animal model of cigarette smoke (CS) –induced chronic obstructive pulmonary disease (COPD) is the primary testing methodology for drug therapies and studies on pathogenic mechanisms of disease. However, researchers have rarely run simultaneous or side-by-side tests of whole-body and nose-only CS exposure in building their mouse models of COPD. We compared and evaluated these two different methods of CS exposure, plus airway Lipopolysaccharides (LPS) inhalation, in building our COPD mouse model. Compared with the control group, CS exposed mice showed significant increased inspiratory resistance, functional residual capacity, right ventricular hypertrophy index, and total cell count in BALF. Moreover, histological staining exhibited goblet cell hyperplasia, lung inflammation, thickening of smooth muscle layer on bronchia, and lung angiogenesis in both methods of CS exposure. Our data indicated that a viable mouse model of COPD can be established by combining the results from whole-body CS exposure, nose-only CS exposure, and airway LPS inhalation testing. However, in our study, we also found that, given the same amount of particulate intake, changes in right ventricular pressure and intimal thickening of pulmonary small artery are a little more serious in nose-only CS exposure method than changes in the whole-body CS exposure method.

Immunological and pathological effects of electronic cigarettes

“…These changes were not induced by ECVs lacking nicotine, thus supporting the direct harmful effects of nicotine. All these inflammatory mediators and enzymes were similarly found to be stimulated in other experiments treating mice with CS …”

“…These data demonstrate that acute exposure to e‐cigarette aerosol in mouse lung induces inflammatory responses. Chronic exposure of mice to nicotine‐containing ECV over a 4‐month period induced respiratory resistance and alveolar airspace enlargement reminiscent of features of COPD, as also found in CS‐exposed mice . Moreover, the nicotine‐containing ECV induced increased levels of IL‐1β and MCP‐1 in the lungs, as well as protease, collagenase and cathepsin expression, all of which are involved in the pathogenesis of COPD.…”

“…Chronic exposure of mice to nicotine-containing ECV over a 4-month period induced respiratory resistance and alveolar airspace enlargement reminiscent of features of COPD, 71 as also found in CS-exposed mice. [72][73][74] Moreover, the nicotine-containing ECV induced increased levels of IL-1β and MCP-1 in the lungs, as well as protease, collagenase and cathepsin expression, all of which are involved in the pathogenesis of COPD. These changes were not induced by ECVs lacking nicotine, thus supporting the direct harmful effects of nicotine.…”

Establishment and evaluation of chronic obstructive pulmonary disease model by chronic exposure to motor vehicle exhaust combined with lipopolysaccharide instillation

“…Emerging evidence suggests that infection and persistent inflammation are key players in the pathogenesis of COPD. Furthermore, our earlier study demonstrated that the combination of LPS and CS causes significant changes in airway inflammation and lung function (Shu et al, 2017). Studies have also reported that the combination of CS and LPS can shorten the period of development of an experimental COPD model (Mizutani et al, 2009;Zhou, Tan, Kuang, Liu, & Wan, 2012).…”

“…As previously described (Shu et al, 2017), the mean linear intercept was determined by counting the diameter of air spaces in 10 random fields per slide to assess alveolar enlargement and destruction. As previously described (Shu et al, 2017), the mean linear intercept was determined by counting the diameter of air spaces in 10 random fields per slide to assess alveolar enlargement and destruction.…”