Sirt-1和Hif-1α在慢性阻塞性肺疾病患者外周血单个核细胞中的表达及其意义

Expressions of Sirt-1 and Hif-1α in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease and their significances

目的:检测慢性阻塞性肺疾病(COPD)患者外周血单个核细胞(PBMCs)中沉默信息调节子(Sirt-1)和缺氧诱导因子1α(Hif-1α)的表达,探讨Sirt-1和Hif-1α的表达在COPD发生发展中的作用。方法:应用肺功能仪对COPD急性加重期组(n=20)、COPD稳定期组(n=22)和对照组(n=20)的研究对象进行肺功能指标测定,采用Real-time PCR和Western blotting法检测3组研究对象PBMCs中Sirt-1和Hif-1αmRNA和蛋白表达,并分析Sirt-1和Hif-1α表达水平与肺功能的关系。结果:与对照组比较,COPD急性加重期组、COPD稳定期组患者第1秒用力呼气容积占预计值百分比(FEV1%)、第1秒用力呼气容积与用力肺活量的比值(FEV1/FVC%)均降低(P<0.05);与COPD稳定期组比较,COPD急性加重期组患者FEV1%和FEV1/FVC%降低(P<0.05)。COPD急性加重期组、COPD稳定期组患者PBMCs中Sirt-1mRNA和蛋白表达水平均低于对照组(P<0.05或P<0.01);与COPD稳定期组比较,COPD急性加重期患者PBMCs中Sirt-1mRNA和蛋白表达水平降低(P<0.01);与对照组比较,COPD患者Hif-1αmRNA及蛋白表达水平均明显升高(P<0.05或P<0.01),COPD急性加重期患者其表达水平升高更明显(P<0.01);与COPD稳定期组比较,COPD急性加重期组患者PBMSCs中Hif-1αmRNA和蛋白表达水平升高(P<0.05)。Pearson直线相关法分析,Sirt-1mRNA(蛋白)表达水平与患者FEV1%(rmRNA=0.61,r蛋白=0.545)和FEV1/FVC%(rmRNA=0.513,r蛋白=0.491)呈正相关关系,Hif-1αmRNA(蛋白)表达水平与FEV1%(rmRNA=-0.812,r蛋白=-0.781)和FEV1/FVC%(rmRNA=-0.661,r蛋白=-0.674)呈负相关关系(P<0.05)。结论:COPD患者PBMCs中Sirt-1基因表达水平下降,Hif-1α基因表达水平上调,二者的表达变化可能与COPD的发生发展密切相关。

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-1and Hif-1αmRNA 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-1and Hif-1αand 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-1mRNA 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-1mRNA 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-1αmRNA 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-1αmRNA 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%（rmRNA =0.661,rprotein=0.545）and FEV1/FVC（rmRNA=0.513,rprotein=0.491）（P〈0.05）,and there were negative correlations between the expression of Hif-1αmRNA（pretein）and FEV1%（rmRNA =-0.812,rprotein=-0.781）and FEV1/FVC（rmRNA=-0.661,rprotein=-0.674）（P〈0.05）.Conclusion The expression level of Sirt-1gene is decreased and the expression level of Hif-1αgene is increased in the patients with COPD,which may be associated with the incidence and pathogenesis of COPD.