Dynamic changes of lung sRAGE in mice with chronic obstructive pulmonary disease induced by cigarette smoke exposure

To study the changes of lung function, pathophysiology, inflammatory cytokines and related inflammatory responses in COPD mouse model, and to analyze the role of sRAGE in the pathogenesis of COPD induced by cigarette smoke (CS) exposure in mice.

24 healthy male C57BL/6J mice aged 6 to 8 weeks were randomly divided into Smoke-Exposed (SE) group and Control group. The mice in SE group were exposed to 7 time points at 3, 7, 15, 30, 60, 90 and 120 days, while mice in control group were exposed to fresh room air, with 3 mice in each group. Lung function of mice was detected at different exposure time points, and the lung tissue sections were stained with HE to observe the lung histopathological changes of mice in each group, and the lung tissue morphological quantitative analysis was performed to evaluate the degree of emphysema. The content of inflammatory cytokines including IL-1β, IL-6 and TNF-α in the supernatant of BALF was detected by ELISA to evaluate the pulmonary inflammation of mice. The expression of sRAGE in BALF supernatant was detected by ELISA. BALF cell precipitates were classified and counted under light microscope.

After 90 days of exposure to cigarette smoke, the lung function of mice was significantly reduced, emphysema appeared significantly, and the expression of inflammatory cells and inflammatory cytokines in BALF was significantly increased (all P<0.05). sRAGE increased significantly in the early stage of CS exposure (7-15 days) compared with the control group, and the number of macrophages and levels of inflammatory cytokines in BALF also increased temporarily (P<0.05). With the gradual exposure of CS, sRAGE expression gradually decreased, and was significantly reduced after COPD formation compared with the control group.

In the process of the occurrence and development of chronic obstructive pulmonary disease induced by cigarette smoke exposure, the level of sRAGE in bronchoalveolar lavage fluid showed a dynamic change of first increase and then decrease. The expression of sRAGE increased in the early stage of smoke exposure and played a transient pro-inflammatory role. With long-term exposure to cigarette smoke, the inflammatory response is gradually aggravated in lung, and the expression of sRAGE is significantly decreased, and its reduction degree is closely related to the degree of reduced lung function and inflammation.