| Objective: In this study,a COPD mice model was established to observe the aging of COPD lung tissue and to investigate whether quercetin could play a therapeutic role in delaying lung aging in COPD and its possible mechanisms.Methods:1.The correlation between COPD and cellular senescence was first investigated by bioinformatics analysis,and gene expression profiles of non-COPD and COPD patients was obtained from the GEO database GSE29133 dataset,and cellular senescence-related genes were obtained from the OMIM database(https://www.omim.org/);2.A randomization method was used to divide the thirty mice into three groups,Con,COPD,and Qu.Establishing the COPD mice model,intra-airway lipopolysaccharide drips were given to both the COPD and Qu groups on days 1 and 14,followed by fumigation for the remaining 28 days.The Qu group received quercetin(50mg/kg)via gavage once a day for 28 days beginning on day 31;the Con and COPD groups were given an equivalent amount of saline.On day 59,all mice were killed,and specimens were gathered and the following tests were conducted: HE staining was employed to observe the pathological alterations of lung tissues,and the extent of lung pathological harm was compared by computing the lung tissue damage score;SA-β-gal staining was used to observe the aging situation of lung tissues;IHC was utilized to assess the expression of Bcl-2 and Bax proteins;Western blot was employed to measure the expression levels of p53,p21 and Rb proteins,and to evaluate the correlation between SA-β-gal positive area and p53,p21 and Rb proteins.Results:1.The differential expression of aging-related genes between non-COPD and COPD patients show an association between cellular senescence and the occurrence of COPD.2.Effect of quercetin on pathological changes of lung histology in COPD mice model: Alveolar walls in COPD mice were damaged and fused together,the alveolar lumen was expanded,there were numerous inflammatory cells in the alveolar lumen,and the alveolar wall was thickened and hemorrhaged when compared to the Control group.Bronchial mucosa epithelial cilia were inverted and disappeared,the wall was thicker,the lumen was deformed,and there were more cupped cells than usual.The lung tissue damage scores of the Con,COPD,and Qu groups were(1.40±0.55),(12.00±1.58)and(7.20±0.84),respectively,and the COPD group had considerably greater lung tissue damage ratings than the Con group,but the Qu group had significantly lower lung tissue damage scores than the COPD group.3.The effect of quercetin on the positive area of SA-β-gal in lung tissue of COPD mice model: the positive area of SA-β-gal was higher in the COPD group compared with the Con group;after quercetin intervention,the positive area of SA-β-gal was lower in the Qu group compared with the COPD group.4.Effects of quercetin on the expression of apoptosis-related proteins Bcl-2 and Bax in COPD mice lung tissues: the COPD group displayed a decrease in Bcl-2 and an increase in Bax compared to the Con group;the Qu group displayed an increase in Bcl-2 and a decrease in Bax compared to the COPD group.5.Effects of quercetin on p53,p21,Rb protein expression in lung tissue of COPD mice model: The COPD mice model revealed a significant increase in p53,p21,Rb protein expression than Con group;conversely,compared with COPD group,the Qu group exhibited a significantly decreased expression of these proteins.A significant positive correlation between SA-β-gal positive area and p53(r = 0.917,P < 0.01),p21(r = 0.867,P < 0.01),Rb(r = 0.867,P < 0.01)expression levels and in mice lung tissue was revealed by correlation analysis.Conclusion:1.Accelerated lung tissue aging in COPD mice;2.Increased apoptosis in lung tissue of COPD mice;3.The p53 signaling pathway may be involved in regulating lung tissue aging and apoptosis in COPD mice;4.Quercetin may play a protective role in reducing lung tissue pathological damage,inhibiting apoptosis and delaying lung tissue aging by downregulating the p53 signaling pathway. |
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