Expression Of NR-026690 In Sputum Macrophages Of Patients With Chronic Obstructive Pulmonary Disease And Its Relationship With Mucus

Object:Chronic obstructive pulmonary disease(COPD)is a common and highly fatal chronic airway inflammatory disease,especially in the acute exacerbation of COPD(AECOPD),which causes quality of life deteriorates and the mortality increases sharply.However,the molecular mechanism of airway inflammation and mucus hypersecretion of AECOPD remains unclear.The aim of the study was to determine the relative expression of long noncoding RNA NR-026690 and EPAC1 in sputum macrophages and peripheral blood mononuclear cell(PBMC)from patients with AECOPD before and after treatment,and analysis the relationship with airway inflammation and mucus hypersecretion.Besides,it aims to to clarify the molecular mechanism of high COPD airway inflammation and mucus secretion by NR-026690 and provide theoretical basis for the diagnosis and treatment of patients with AECOPD.Methods:A total of 25 COPD patients admitted to the Respiratory and Critical Care Department of Qingdao Municipal Hospital due to acute exacerbation were included.Patients were given standard treatment according to GOLD 2019,and their peripheral blood and induced sputum were collected before and after treatment.Quantitative real time polymerase chain reaction(q RT-PCR)was used to detect the relative expression of NR-026690 and EPAC1 in PBMC and induced sputum macrophages.The relative expression of EPAC1 in sputum macrophages was detected by immunohistochemistry.The concentrations of MUC5 AC,IL-6,IL-8 and TNF-α in the supernatant of induced sputum were detected by enzyme linked immunosorbent assay(ELISA).The correlation between MUC5 AC and IL-6,IL-8,TNF-α were analyzed by Pearson correlation,as well as the changes before and after treatment were analyzed by Pearson correlation.Results:1.The sputum symptom scores of AECOPD were significantly decreased after treatment(P<0.001),and the concentration of C-reactive protein(CRP)was significantly decreased after treatment(P<0.006).2.The relative expression of NR-026690 in PBMC and induced sputum macrophages of AECOPD patients was significantly decreased after treatment(P<0.001,=0.004).3.The concentration of MUC5 AC in induced sputum supernatant of AECOPD patients decreased significantly after treatment(P=0.003);The concentration of IL-6 in induced sputum supernatant of AECOPD patients decreased significantly after treatment(P<0.001),while the change of IL-6 before and after treatment was positively correlated with the change of MUC5 AC before and after treatment(r=0.481,P=0.023);The concentration of IL-8 in induced sputum supernatant of AECOPD patients decreased significantly after treatment(P=0.027),while there was no correlation between the change of IL-8 before and after treatment and the change of MUC5 AC before and after treatment(r=0.410,P=0.058);The concentration of TNF-α in induced sputum supernatant of AECOPD patients decreased significantly after treatment(P=0.002),while there was no correlation between the change of TNF-α before and after treatment and the change of MUC5 AC before and after treatment(r=-0.249,P=0.264).4.Before treatment,the relative expression level of NR-026690 in sputum macrophages was positively correlated with the level of IL-6 in sputum supernatant(r=0.592,P=0.004),and also had a positive correlation trend with the level of MUC5 AC in sputum supernatant,although there was no statistical significance(r=0.402,P=0.064).The change of NR-026690 in sputum macrophages before and after treatment were positively correlated with the change of IL-6 and MUC5 AC in sputum supernatant(r=0.454,0.476,P=0.034,0.025).5.The relative expression level of EPAC1 in induced sputum macrophages of AECOPD patients after treatment was significantly higher than that of before treatment(P=0.020),and was negatively correlated with the relative expression level of NR-026690(r=-0.483,P=0.023);Immunohistochemical results showed that EPAC1 protein was positively expressed in sputum macrophages before and after treatment,and the expression of EPAC1 was increased after treatment compared with that before treatment.6.Before treatment,the relative expression level of EPAC1 in sputum macrophages was negatively correlated with the concentration of IL-6 in sputum supernatant(r=-0.495,P=0.019),and also had a negative correlation trend with the level of MUC5 AC in sputum supernatant,although there was no statistical significance(r=-0.413,P=0.056).The change of EPAC1 in sputum macrophages before and after treatment were negatively correlated with the change of IL-6 and MUC5 AC in sputum supernatant(r=-0.445,0.513,P=0.038,0.015).Conclusions:1.After treatment,the expression of NR-026690 decreases,the expression of EPAC1 increases,and the concentration of inflammatory factors such as IL-6,IL-8,TNF-αand MUC5 AC decreased in patients with AECOPD.2.Airway inflammation and mucus hypersecretion were improved in patients withAECOPD after treatment,which may be related to NR-026690 and EPAC1.