The Expression And Significance Of NGAL MRNA And MMP-9 MRNA In Peripheral Blood Mononuclear Cells In Patients With Chronic Obstructive Pulmonary Disease

Objective:The pathogenesis of chronic obstructive pulmonary disease（COPD）is still not fully understood.Inflammatory response,protease-antiprotease imbalance,oxidative stress,and so on may jointly promote the pathological changes of COPD.Therefore,the search for inflammatory mediators at key sites will play a catalytic role in exploring the pathogenesis of COPD and developing more targeted treatment protocols.This study was conducted to investigate the expression levels of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells from AECOPD patients before and after treatment,stable COPD patients and control group,and analysis their correlation with clinical indicators of COPD patients,to explore the role and significance of NGAL and MMP-9 in the pathogenesis of COPD.Methods:From November 2016 to July 2017,patients with COPD who were admitted to the clinic department and inpatient department of Respiratory Medicine of the Affiliated Hospital of Northern Sichuan Medical College were selected as the study subjects.Among them,25 patients were matched before and after treatment with acute exacerbation of COPD（AECOPD）,18 males and 7 females,with an average age of（72.08±8.32）years.Patients with AECOPD who had stable or mild symptoms after treatment such as anti-infection,spasmolytic,and oxygen inhalation were considered to have entered a stable state.There were 80 patients with stable COPD（SCOPD）,including 50 males and 30 females,with an average age of（68.16±8.23）years.According to the comprehensive assessment results,the patients in the SCOPD group were divided into low-risk group B and high-risk group D.There were 34 cases in group B and 38 cases in group D.40 healthy subjects in the same period were selected as the control group,including 25 males and 15 females,with an average age of（63.70±10.18）years.Peripheral venous blood samples were collected from all subjects.The expression levels of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells were measured by real-time fluorescence quantitative PCR.The differences in expression of NGAL mRNA and MMP-9 mRNA between different groups were compared and analyzed.The relationship between NGAL mRNA and MMP-9 mRNA expression levels and their correlation with clinical indicators such as body mass index,smoking index,blood routine and lung function were analyzed.Results:（1）The relative expressions of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells of AECOPD group was 0.00802（0.00287,0.04477）,0.01119（0.00354,0.02891）,which was higher than that of SCOPD group 0.00464（0.00121,0.01276）,0.00439（0.00155,0.00990）and Control group 0.00200（0.00142,0.00401）,0.00195（0.00062,0.00314）,and SCOPD group was higher than the control group,the difference was statistically significant（all P<0.01）.（2）The relative expressions of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells after AECOPD treatment were 0.00446（0.00123,0.02304）,0.00536（0.00144,0.02711）lower than before treatment0.00802（0.00287,0.04477）,0.01119（0.00354,0.02891）,the difference was statistically significant（all P<0.01）.（3）The relative expressions of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells from patients with AECOPD and respiratory failure were 0.01852（0.00721,0.05373）,0.01769（0.00473,0.05722）,which were higher than that of patients without respiratory failure0.00287（0.00131,0.02147）,0.00472（0.00228,0.01433）,the difference was statistically significant（all P<0.05）.（4）The relative expressions of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells in the low-risk group B patients in the SCOPD group were 0.00300（0.00117,0.00683）,0.00348（0.00154,0.00737）lower than the high-risk group D patients 0.00604（0.00302,0.01899）,0.00834（0.00242,0.02376）,the difference was statistically significant（all P<0.05）.（5）There was a significant positive correlation between NGAL mRNA and MMP-9 mRNA expression in peripheral blood mononuclear cells in patients with AECOPD and SCOPD,and the correlation was statistically significant（r=0.831,P<0.01;r=0.764,P<0.01）.（6）The relative expressions of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells in patients with SCOPD were negatively correlated with the lung function FEV₁%pred,and the correlation was statistically significant（r=-0.416,P<0.01;r=-0.312,P<0.05）.（7）The relative expressions of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells in AECOPD and SCOPD patients were positively correlated with the number of leukocytes,the number of neutrophils,and the percentage of neutrophils,and the correlation was statistically significant（all P<0.05）.The relative expressions of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells in patients with SCOPD were not significantly correlated with clinical indicators such as body mass index,smoking index,and FEV₁/FVC,etc.（all P>0.05）.Conclusion:（1）Compared with the healthy control group,the relative expression of NGAL mRNA and MMP-9 m RNA in SCOPD group increased,and the AECOPD group increased more significantly,and decreased after treatment.It is speculated that NGAL and MMP-9 are involved in the occurrence of COPD and promote the development of COPD.（2）With the exacerbation of COPD patients,the increased risk of acute exacerbations and the emergence of complications,the relative expression of NGAL mRNA and MMP-9 mRNA increased accordingly.And NGAL mRNA and MMP-9 mRNA may become new indicators for assessing the condition of COPD and monitoring the treatment response.（3）There was a significant correlation between the relative expression levels of NGAL mRNA and MMP-9 mRNA.The two may interact to promote the inflammatory response of COPD and affect the progression of emphysema.