科研之友
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摘要
AIM: To investigate the potential lung-protective effects of tiotropium(TIO)in a mouse model of chronic obstructive pulmonary disease(COPD)and to explore whether its effects are mediated by inhibition of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome. METHODS: C57BL/6J mice were exposed to cigarette smoke for 6 months to establish a model of COPD. The mice were randomly divided into 3 groups: saline control group, cigarette smoke exposure group(COPD group), and cigarette smoke with TIO treatment(COPD+TIO)group, with 6 mice in each group. The mice were monitored for changes in general condition, lung function, pathological and inflammatory cells in the lungs. Enzyme-linked immunosorbent assay(ELISA)was used to measure the protein levels of interleukin(IL)-1β and IL-18 in the bronchoalveolar lavage fluid(BALF), and Western blot was used to detect the protein levels of NLRP3 and caspase-1 in the lung tissues. RESULTS: Exposure to cigarette smoke resulted in significant decreases in lung function parameters, including forced expiratory volume in 100 ms(FEV100), FEV100/forced vital capacity(FVC)and dynamic lung compliance(Cdyn), as well as an increase in resistance index(RI)compared with control group(P<0. 05). Additionally, the mice in COPD group exhibited decreased body weight and increased mean linear intercept in lung histopathology(P<0. 05), but no significant difference in FVC compared with control group. Inflammatory cell infiltration, and the levels of IL-1β and IL-18 in BALF were dramatically increased in COPD group(P<0. 05). Furthermore, NLRP3 and caspase-1 protein levels were increased in lung tissues of COPD group(P<0. 05). Treatment with TIO attenuated the lung function decline, with increased FEV100 and FEV100/FVC, and decreased RI compared with COPD group(P<0. 05). There were no significant differences in body weight, FVC and Cdyn between COPD group and COPD+TIO group. Treatment with TIO also reduced mean linear intercept in lung histopathology, inflammatory cell infiltration, IL-1β and IL-18 levels in BALF, and NLRP3 and caspase-1 expression in lung tissue(P<0. 05). CONCLUSION: Treatment with TIO may exert protective effects on cigarette smoke-induced lung function decline and inflammation in a mouse model of COPD, potentially through the inhibition of NLRP3 inflammasome in lungs. ? 2023 Editorial Board of Chinese Journal of Pathophysiology.
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