Molecular mechanism of rapamycin-induced autophagy activation to attenuate smoking-induced COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the severe lung and respiratory airway disorders, with high prevalence rate in China. In this paper, we employed network pharmacology predictions to identify autophagy as a signaling pathway associated with COPD. To explore the protective effect of autophagy against COPD and its specific mechanism, we established a mouse model of COPD and administered 3-methyladenine (3-MA) and rapamycin (RAPA) to intervene in autophagy. The lung function of the mice was assessed using an animal pulmonary function analysis system, and lung tissue structure was evaluated through hematoxylin and eosin (HE) staining. The TUNEL staining method was employed to determine the level of apoptosis in lung tissue. Western blot analysis was conducted to measure the expression of autophagy and apoptosis-related proteins, while RT-qPCR was used to assess the expression of apoptosis-related mRNA. The results showed that RAPA effectively improved lung function, attenuated pathological lung injury and increased autophagy level in COPD mice. Apoptosis analysis showed that the apoptosis rate was elevated in COPD and 3- MA mice, whereas it was significantly reduced in RAPA mice. Our findings suggest that stimulation of autophagy may be a potential therapy for the future treatment of COPD.