Abstract:

Objective To investigate the expressions of silent information regulator 1 (Sirt-1) and hypoxia-inducible factor 1α (Hif-1α) in peripheral blood mononuclear cells (PBMCs) of the chronic obstructive pulmonary disease (COPD) patients,and to clarify their potential roles in the occurrence and development of COPD.Methods 42 patients with COPD in acute exacerbation stage (n=20) and in stable stage (n=22) and 20 healthy people were chosen.The lung function indexes of all cases were examined by lung function machine.The expressions of Sirt-1 and Hif-1α mRNA and protein in PBMCs of the objects in various groups were measured by Real-time PCR and Western blotting method. The relationships between the expression levels of Sirt-1 and Hif-1α and lung function were analyzed.Results Compared with control group,the calculated ratios of forced expiration volume in one second to predicted volume (FEV₁%) and the the calculated ratios of forced expiration volume in one second to forced vital capacity (FEV₁/FVC%) of the patients with COPD in stable stage and acute exacerbation stage were significantly decreased (P<0.05);compared with the patients in stable stage of COPD group,the FEV₁ and FEV₁/FVC% of the patients with COPD in acute exacerbation stage group were decreased (P<0.05).The expression levels of Sirt-1 mRNA and protein of the patients with COPD in acute exacerbation stage and stable stage were significantly lower than those in control group (P<0.05 or P<0.01);compared with the patients in stable stage of COPD group,the expressions of Sirt-1 mRNA and protein in PBMCs of the patients with COPD in acute exacerbation stage group were decreased(P<0.05);meanwhile,the expression levels of Hif-1α mRNA and protein of COPD patients were significantly higher than those in control group (P<0.05, P<0.01),especially in acute exacerbation stage(P<0.01);compared with the patients in stable stage of COPD group,the expressions of Hif-1α mRNA and protein in PBMSCs of the patients with COPD in acute exacerbation stage group were increased(P<0.05).The Pearson correlation analysis results showed that there were positive correlations between the expression levels of Sirt-1 mRNA (protein) and the FEV₁%(r_mRNA=0.661,r_protein=0.545) and FEV₁/FVC (r_mRNA=0.513,r_protein=0.491)(P<0.05),and there were negative correlations between the expression of Hif-1α mRNA (pretein) and FEV₁%(r_mRNA=-0.812,r_protein=-0.781) and FEV₁/FVC(r_mRNA=-0.661,r_protein=-0.674) (P<0.05).Conclusion The expression level of Sirt-1 gene is decreased and the expression level of Hif-1α gene is increased in the patients with COPD,which may be associated with the incidence and pathogenesis of COPD.

Key words: silent information regulator 1, hypoxia-inducible factor 1α, chronic obstructive pulmonary disease, peripheral blood mononuclear cells