Abstract
Chronic obstructive pulmonary disease (COPD) has always attracted global attention with its high prevalence, incidence rate, and mortality. Exposure to cigarette smoke is one of main causes of COPD. Therefore, it is still necessary to study its pathogenesis and find new therapeutic strategies for early COPD prevention and treatment. Vardenafil, a type 5 phosphodiesterase (PDE5) inhibitor, is known to have an efficient therapy in some cardiovascular, pulmonary, and vascular diseases, which is an important mechanism for COPD. However, it still loss relevant research on whether vardenafil is effective in COPD and its mechanism. In this study, the cigarette smoke inhalation was performed to establish cigarette smoke-induced COPD model using C57BL/6 mice and 16HBE cells were treated with cigarette smoke extract (CSE). Mice were treated with vardenafil for 30 d. Then condition of lung injury was evaluated using histological analysis. The content of cytokines and the number of inflammatory cells in lung tissues or bronchoalveolar lavage fluid were measured. Additionally, western blot analysis was employed to evaluate the activation of adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)-mediated autophagy in vitro. The results showed that vardenafil abolished CSE’s effect by activating autophagy via the AMPK/mTOR signalling pathway in vitro. Vardenafil attenuated cigarette smoke-induced lung injury and inflammation response by activating autophagy via the AMPK/mTOR signalling pathway in vivo. These results provide valuable insights into the molecular mechanisms underlying vardenafil’s beneficial effects in cigarette smoke-induced COPD treatment. In conclusion, vardenafil alleviates cigarette smoke-induced experimental COPD by activating autophagy via the AMPK/mTOR signalling pathway.
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Funding
This study was funded by Jing’an District health scientific research project of Shanghai (2018MS05), Shanghai General Hospital Integrated Traditional Chinese and Western Medicine Special Project (ZHYY-ZXYJHZX-202115) and the central transfer payment basic public health service project-creation of health places-construction of smoking cessation outpatient services (in 2023).
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YF and HC conceived and designed the study. WL and JY performed the experiments and wrote the paper. JX, LZ, and CZ did the data analysis and prepared the figures. YW and YW did the references research. HC supervised the study and revised and approved the manuscript. All authors have read and approved the manuscript.
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This study was approved by the ethical committee of Huashan Hospital of Fudan University.
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Li, W., Yan, J., Xu, J. et al. Vardenafil alleviates cigarette smoke-induced chronic obstructive pulmonary disease by activating autophagy via the AMPK/mTOR signalling pathway: an in vitro and in vivo study. In Vitro Cell.Dev.Biol.-Animal 59, 717–728 (2023). https://doi.org/10.1007/s11626-023-00820-z
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DOI: https://doi.org/10.1007/s11626-023-00820-z