AECOPD患者治疗前后外周血单个核细胞NGAL mRNA、MMP-9 mRNA表达差异及临床意义
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摘要
目的:探讨慢性阻塞性肺疾病急性加重期(AECOPD)患者治疗前后外周血单个核细胞NGAL mRNA、MMP-9 mRNA的表达差异及临床意义。方法:前瞻性纳入AECOPD患者25例,其中男18例,女7例,年龄50～86岁,平均(72.1±8.3)岁。采用实时荧光定量PCR技术检测AECOPD患者治疗前后外周血单个核细胞NGAL mRNA、MMP-9 mRNA的表达水平,同时收集患者体质指数、吸烟指数、血常规、肺功能等临床指标,分析NGAL mRNA和MMP-9mRNA与临床指标间的相关性。结果:AECOPD患者治疗后NGAL mRNA和MMP-9 mRNA相对表达量均较治疗前下降,差异有统计学意义(P<0.01)。AECOPD合并呼吸衰竭组患者NGAL mRNA和MMP-9 mRNA相对表达量均高于AECOPD未合并呼吸衰竭组,差异有统计学意义(P<0.05)。NGAL mRNA和MMP-9 mRNA相对表达量间呈显著正相关,差异有统计学意义(r=0.831,P<0.01)。NGAL mRNA和MMP-9 mRNA相对表达量与外周血白细胞总数、中性粒细胞总数和中性粒细胞百分比均呈正相关,差异有统计学意义(P<0.05)。结论:NGAL和MMP-9极有可能参与COPD的发病,其相对表达水平或可用来评估AECOPD病情严重程度和监测患者对治疗的反应。
Objective To investigate the difference expression and clinical significance of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells before and after treatment in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Method 25 patients with AECOPD prospectively,including 18 males and 7 females,aged 50～86 years,mean age(72.1±8.3) years.Real-time fluorescence quantitative PCR was used to detect the expression of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells before and after treatment in patients with AECOPD.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 The relative expression of NGAL mRNA and MMP-9 mRNA in AECOPD patients after treatment was lower than before treatment,and the difference was statistically significant(P<0.01).The relative expression of NGAL mRNA and MMP-9 mRNA in AECOPD patients with respiratory failure were higher than those in patients without respiratory failure,the difference was statistically significant(P<0.05).There was a significant positive correlation between the relative expression levels of NGAL mRNA and MMP-9 mRNA,the difference was statistically significant(r=0.831,P<0.01).The relative expression of NGAL mRNA and MMP-9 mRNA was positively correlated with the total number of white blood cells,the total number of neutrophils and the percentage of neutrophils in peripheral blood,and the correlation was statistically significant(P<0.05).Conclusion NGAL and MMP-9 are highly likely to be involved in the onset of COPD,and their relative expression levels may be used to assess the severity of AECOPD and monitor the patient′s response to treatment.
Objective To investigate the difference expression and clinical significance of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells before and after treatment in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Method 25 patients with AECOPD prospectively,including 18 males and 7 females,aged 50～86 years,mean age(72.1±8.3) years.Real-time fluorescence quantitative PCR was used to detect the expression of NGAL mRNA and MMP-9 mRNA in peripheral blood mononuclear cells before and after treatment in patients with AECOPD.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 The relative expression of NGAL mRNA and MMP-9 mRNA in AECOPD patients after treatment was lower than before treatment,and the difference was statistically significant(P<0.01).The relative expression of NGAL mRNA and MMP-9 mRNA in AECOPD patients with respiratory failure were higher than those in patients without respiratory failure,the difference was statistically significant(P<0.05).There was a significant positive correlation between the relative expression levels of NGAL mRNA and MMP-9 mRNA,the difference was statistically significant(r=0.831,P<0.01).The relative expression of NGAL mRNA and MMP-9 mRNA was positively correlated with the total number of white blood cells,the total number of neutrophils and the percentage of neutrophils in peripheral blood,and the correlation was statistically significant(P<0.05).Conclusion NGAL and MMP-9 are highly likely to be involved in the onset of COPD,and their relative expression levels may be used to assess the severity of AECOPD and monitor the patient′s response to treatment.
引文
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[10] 胡玲玲,戈艳蕾,黄超,等.a慢性阻塞性肺疾病患者血浆中性粒细胞明胶酶蛋白及内皮素-1水平与认知功能障碍的相关性[J].中华行为医学与脑科学杂志,2016,(9):817.
[11] Libra M,Scalisi A,Vella N,et al.Uterine cervical carcinoma:role of matrix metalloproteinases[J].Int J Oncol,2009,34(4):897.
[12] 李洋.矽肺病患者血清TNF-α与MMP-9的早期诊断价值[J].吉林医学,2016,37(12):2880.
[13] Chaudhuri R,McSharry C,Spears M,et al.Sputum matrix metalloproteinase-9 is associated with the degree of emphysema on computed tomography in COPD[J].Transl Respir Med,2013,1(1):11.
[14] Mercer P F,Shute J K,Bhowmik A,et al.MMP-9,TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation[J].Respiratory Research,2005,6(1):151.
[15] Bchir S,Nasr HB,Bouchet S,et al.Concomitant elevations of MMP-9,NGAL,proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease[J].J Cell Mol Med,2017,21(7):1280.
[2] Candido S,Maestro R,Polesel J,et al.Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer[J].Oncotarget,2014,5(6):1576.
[3] 中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2013年修订版)[J].中华结核和呼吸杂志,2013,(4):255.
[4] Lopez-Campos JL,Tan W,Soriano JB.Global burden of COPD[J].Respirology,2016,21(1):14.
[5] Woodruff PG.Novel outcomes and end points:biomarkers in chronic obstructive pulmonary disease clinical trials[J].Proc Am Thorac Soc,2011,8(4):350.
[6] Flo TH,Smith KD,Sato S,et al.Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron[J].Nature,2004,432(7019):917.
[7] 肖锐,陈荣昌.中性粒细胞明胶酶相关脂质运载蛋白在小鼠呼吸机所致肺损伤模型中的表达[J].中国病理生理杂志,2013,(10):1753.
[8] Eagan TM,Damas JK,Ueland T,et al.Neutrophil gelatinase-associated lipocalin:a biomarker in COPD[J].Chest,2010,138(4):888.
[9] Wang XR,Li YP,Gao S,et al.Increased serum levels of lipocalin-1 and -2 in patients with stable chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2014,9:543.
[10] 胡玲玲,戈艳蕾,黄超,等.a慢性阻塞性肺疾病患者血浆中性粒细胞明胶酶蛋白及内皮素-1水平与认知功能障碍的相关性[J].中华行为医学与脑科学杂志,2016,(9):817.
[11] Libra M,Scalisi A,Vella N,et al.Uterine cervical carcinoma:role of matrix metalloproteinases[J].Int J Oncol,2009,34(4):897.
[12] 李洋.矽肺病患者血清TNF-α与MMP-9的早期诊断价值[J].吉林医学,2016,37(12):2880.
[13] Chaudhuri R,McSharry C,Spears M,et al.Sputum matrix metalloproteinase-9 is associated with the degree of emphysema on computed tomography in COPD[J].Transl Respir Med,2013,1(1):11.
[14] Mercer P F,Shute J K,Bhowmik A,et al.MMP-9,TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation[J].Respiratory Research,2005,6(1):151.
[15] Bchir S,Nasr HB,Bouchet S,et al.Concomitant elevations of MMP-9,NGAL,proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease[J].J Cell Mol Med,2017,21(7):1280.