慢性阻塞性肺疾病急性加重期吸烟者血清MMP-9、NGAL和proMMP-9/NGAL的表达关系及意义
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摘要
目的探究慢性阻塞性肺疾病急性加重期(AECOPD)吸烟者血清基质金属蛋白酶9(MMP-9)、中性粒细胞明胶酶相关载脂蛋白(NGAL)和proMMP-9/NGAL复合物的表达关系及意义。方法选择2016年5月至2017年5月就诊的AECOPD患者78例为研究对象;另选择进行体检的健康者60例作为健康对照组。肺功能仪测定COPD患者第1秒用力呼气容积(FEV1)、用力肺活量(FVC)及FEV1/FVC等肺功能指标;采用酶联免疫(ELISA)方法分别检测各组受试者血清中MMP-9、NGAL、proMMP-9/NGAL水平,同时分析血清中MMP-9、NGAL、proMMP-9/NGAL水平相关性及其与吸烟指数的关系。结果肺功能仪结果显示,AECOPD组患者肺功能指标FEV1、FVC、FEV1/FVC值较健康对照组均显著降低(P <0. 05),且AECOPD组肺功能指标FEV1/FVC <70%。ELISA结果显示,AECOPD组血清中MMP-9、NGAL、proMMP-9/NGAL水平较健康对照组均明显升高(P <0. 05);健康吸烟组、AECOPD不吸烟组与AECOPD吸烟组血清中MMP-9、NGAL、proMMP-9/NGAL水平较健康不吸烟组均明显升高(P <0. 05); AECOPD不吸烟组与AECOPD吸烟组血清中MMP-9、NGAL、proMMP-9/NGAL水平较健康吸烟组均明显升高(P <0. 05); AECOPD吸烟组血清中MMP-9、NGAL、proMMP-9/NGAL水平较AECOPD不吸烟组均明显升高(P <0. 05)。AECOPD患者血清中MMP-9水平与NGAL、proMMP-9/NGAL均呈正相关关系(P <0. 05),血清中NGAL水平与proMMP-9/NGAL亦呈正相关关系(P <0. 05)。健康≥400年支组、AECOPD <400年支组与AECOPD≥400年支组血清中MMP-9、NGAL、proMMP-9/NGAL水平较健康<400年支组均明显升高(P <0. 05); AECOPD <400年支组与AECOPD≥400年支组血清中MMP-9、NGAL、proMMP-9/NGAL水平较健康≥400年支组均明显升高(P <0. 05); AECOPD≥400年支组血清中MMP-9、NGAL、proMMP-9/NGAL水平较AECOPD <400年支组均明显升高(P <0. 05)。结论 AECOPD患者血清中MMP-9、NGAL、proMMP-9/NGAL水平显著升高,且与吸烟指数有关,可作为AECOPD病情的监测指标。
Objective To investigate the expression and signioficance of serum matrix metalloproteinase 9(MMP-9),neutrophil gelatinase associated apolipoprotein(NGAL) and proMMP-9/NGAL in smoking patients with acute exacerbation chronic obstructive pulmonary disease(AECOPD). Methods A total of 78 patients with AECOPD who were treated in our hospital from May 2016 to May 2017 were enrolled as AECOPD group in the study,at the same time,the other60 healthy persons who underwent physical examination in our hospital were enrolled as control group. The forced expiratory volume(FEV1) in the first second,forced vital capacity(FVC),and FEV1/FVC pulmonary function indexes were detected by using pulmonary function test instrument. Moreover the serum levels of MMP-9,NGAL and proMMP-9/NGAL were detected by enzyme linked immunosorbent assay(ELISA),and the correlation of MMP-9,NGAL and proMMP-9/NGAL levels and their relationship with smoking index was analyzed. Results The lung function examination results showed that the lung function indexes including FEV1,FVC and FEV1/FVC in AECOPD group were significantly lower than those in control group(P <0. 05),and FEV1/FVC was less than 70% in AECOPD group. The ELISA results showed that the serum levels of MMP-9,NGAL and proMMP-9/NGAL in AECOPD group were significantly higher than those in control group(P < 0. 05). Moreover the serum levels of MMP-9,NGAL and proMMP-9/NGAL were significantly increased in non-smoking AECOPD group and smoking AECOPD group,as compared with those in healthy non-smoking group(P < 0. 05). In addition the serum levels of MMP-9 in AECOPD group were positively correlated with those of NGAL and proMMP-9/NGAL(P < 0. 05),and the serum levels of NGAL were positively correlated with thoesof proMMP-9/NGAL(P < 0. 05). Besides the serum levels of MMP-9,NGAL and proMMP-9/NGAL in health smoking group(≥400 cigarettes per year),AECOPD smoking group(< 400 cigarettes per year) and AECOPD smoking group(≥400 cigarettes per year) were significantly increased,as compared with those in health smoking group(< 400 cigarettes per year)(P <0. 05),and the serum levels of MMP-9,NGAL and proMMP-9/NGAL in AECOPD smoking group(< 400 cigarettes per year)and AECOPD smoking group(≥ 400 cigarettes per year) were significantly increased,as compared with those in health smoking group(≥400 cigarettes per year)(P < 0. 05). Furthermore the serum levels of MMP-9,NGAL and proMMP-9/NGAL AECOPD AECOPD smoking group(≥400 cigarettes per year) were significantly higher than those AECOPD smoking group(< 400 cigarettes per year)(P < 0. 05). Conclusion The serum levels of MMP-9,NGAL and proMMP-9/NGAL in patients with AECOPD are significantly increased,which is related to smoking index,thus,these indexes can be regarded as the monitoring indexes for AECOPD disease condition.
Objective To investigate the expression and signioficance of serum matrix metalloproteinase 9(MMP-9),neutrophil gelatinase associated apolipoprotein(NGAL) and proMMP-9/NGAL in smoking patients with acute exacerbation chronic obstructive pulmonary disease(AECOPD). Methods A total of 78 patients with AECOPD who were treated in our hospital from May 2016 to May 2017 were enrolled as AECOPD group in the study,at the same time,the other60 healthy persons who underwent physical examination in our hospital were enrolled as control group. The forced expiratory volume(FEV1) in the first second,forced vital capacity(FVC),and FEV1/FVC pulmonary function indexes were detected by using pulmonary function test instrument. Moreover the serum levels of MMP-9,NGAL and proMMP-9/NGAL were detected by enzyme linked immunosorbent assay(ELISA),and the correlation of MMP-9,NGAL and proMMP-9/NGAL levels and their relationship with smoking index was analyzed. Results The lung function examination results showed that the lung function indexes including FEV1,FVC and FEV1/FVC in AECOPD group were significantly lower than those in control group(P <0. 05),and FEV1/FVC was less than 70% in AECOPD group. The ELISA results showed that the serum levels of MMP-9,NGAL and proMMP-9/NGAL in AECOPD group were significantly higher than those in control group(P < 0. 05). Moreover the serum levels of MMP-9,NGAL and proMMP-9/NGAL were significantly increased in non-smoking AECOPD group and smoking AECOPD group,as compared with those in healthy non-smoking group(P < 0. 05). In addition the serum levels of MMP-9 in AECOPD group were positively correlated with those of NGAL and proMMP-9/NGAL(P < 0. 05),and the serum levels of NGAL were positively correlated with thoesof proMMP-9/NGAL(P < 0. 05). Besides the serum levels of MMP-9,NGAL and proMMP-9/NGAL in health smoking group(≥400 cigarettes per year),AECOPD smoking group(< 400 cigarettes per year) and AECOPD smoking group(≥400 cigarettes per year) were significantly increased,as compared with those in health smoking group(< 400 cigarettes per year)(P <0. 05),and the serum levels of MMP-9,NGAL and proMMP-9/NGAL in AECOPD smoking group(< 400 cigarettes per year)and AECOPD smoking group(≥ 400 cigarettes per year) were significantly increased,as compared with those in health smoking group(≥400 cigarettes per year)(P < 0. 05). Furthermore the serum levels of MMP-9,NGAL and proMMP-9/NGAL AECOPD AECOPD smoking group(≥400 cigarettes per year) were significantly higher than those AECOPD smoking group(< 400 cigarettes per year)(P < 0. 05). Conclusion The serum levels of MMP-9,NGAL and proMMP-9/NGAL in patients with AECOPD are significantly increased,which is related to smoking index,thus,these indexes can be regarded as the monitoring indexes for AECOPD disease condition.
引文
1王少飞,张庆,张勃,等.戒烟干预对不同性别吸烟慢性阻塞性肺疾病患者临床症状及肺通气功能的影响研究.中国全科医学,2013,16:136-139.
2 Wain LV,Shrine N,Miller S,et al. Novel insights into the genetics of smoking behaviour,lung function,and chronic obstructive pulmonary disease(UK BiLEVE):a genetic association study in UK Biobank.Lancet Respiratory Medicine,2015,3:769-781.
3 夏杰,谢俊刚,徐永健.慢性阻塞性肺疾病发病机制的研究进展.国际呼吸杂志,2014,34:53-57.
4 Leppert D,Ford J,Stabler G,et al. Matrix metalloproteinase-9(gelatinase B)is selectively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain,2017,121:2327-2334.
5 孙晓钰,杨瑞青,王保贵.中性粒细胞明胶酶相关脂质运载蛋白在慢性阻塞性肺疾病急性加重期的表达.临床肺科杂志,2017,22:679-682.
6 Bchir S,Nasr HB,Bouchet S,et al. Concomitant elevations of MMP-9,NGAL,pro MMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease. Journal of Cellular&Molecular Medicine,2017,21:1280-1291.
7 Global Initiative for Chronic Obstructive Lung Disease. GOLD 2017Global Strategy for the Diagnosis,Management and Prevention of COPD.
8 宣萱,李艳.降钙素原、超敏C反应蛋白、D-二聚体和纤维蛋白原在COPD急性加重期患者的动态变化及临床意义.临床和实验医学杂志,2015,14:202-204.
9 Lim JU,Lee JH,Ju SK,et al. Comparison of World Health Organization and Asia-Pacific body mass index classifications in COPD patients.International Journal of Chronic Obstructive Pulmonary Disease,2017,12:2465-2475.
10 胡国平,钟南山,冉丕鑫.中国的大气污染和COPD.中国胸心血管外科临床杂志,2016,23:107-112.
11 唐文芳,刘日辉,于雅琴,等. 2000-2014年中国40岁以上成人慢性阻塞性肺疾病患病率的Meta分析.吉林大学学报(医学版),2015,41:961-968.
12 Valacchi G,Maioli E,Sticozzi C,et al. Exploring the link between scavenger receptor B1 expression and chronic obstructive pulmonary disease pathogenesis. Annals of the New York Academy of Sciences,2015,1340:47-54.
13 Tse HN,Tseng CZS. Update on the pathological processes,molecular biology,and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease,2014,9:825-836.
14 官秋玥,向征.慢性阻塞性肺疾病中蛋白酶与抗蛋白酶系统的研究进展.国际呼吸杂志,2014,36:1185-1188.
15 高振,李风森,王晶,等.寒燥对慢性阻塞性肺疾病模型肺部蛋白酶-抗蛋白酶失衡的影响.中华中医药杂志,2014,29:3773-3777.
16 Sundar IK,Hwang JW,Wu S,et al. Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation. Biochemical&Biophysical Research Communications,2011,406:127-133.
17 Grzela K,Litwiniuk M,Zagorska W,et al. Airway remodeling in chronic obstructive pulmonary disease and asthma:the role of matrix metalloproteinase-9. Archivum Immunologiae Et Therapiae Experimentalis,2016,64:1-9.
18 张平,朱应群,李喆,等.维生素D与基质金属蛋白酶-9在慢性阻塞性肺疾病中的表达及相关性分析.国际呼吸杂志,2014,34:649-651.
19 Grzela K,Litwiniuk M,Zagorska W,et al. Airway remodeling in chronic obstructive pulmonary disease and asthma:the role of matrix metalloproteinase-9. Archivum Immunologiae Et Therapiae Experimentalis,2016,64:1-9.
20 Gilet A,Zou F,Boumenir M,et al. Aldosterone up-regulates MMP-9 and MMP-9/NGAL expression in human neutrophils through p38,ERK1/2and PI3K pathways. Experimental Cell Research,2014,331:152-63.
21 孙晓钰,杨瑞青,王保贵.中性粒细胞明胶酶相关脂质运载蛋白在慢性阻塞性肺疾病急性加重期的表达.临床肺科杂志,2017,22:679-682.
22 Vanessa A,Morena S,Javier C,et al. The potential of lipocalin-2/NGAL as biomarker for inflammatory and metabolic diseases:. Biomarkers:biochemical indicators of exposure,response,and susceptibility to chemicals,2015,20:565-571.
2 Wain LV,Shrine N,Miller S,et al. Novel insights into the genetics of smoking behaviour,lung function,and chronic obstructive pulmonary disease(UK BiLEVE):a genetic association study in UK Biobank.Lancet Respiratory Medicine,2015,3:769-781.
3 夏杰,谢俊刚,徐永健.慢性阻塞性肺疾病发病机制的研究进展.国际呼吸杂志,2014,34:53-57.
4 Leppert D,Ford J,Stabler G,et al. Matrix metalloproteinase-9(gelatinase B)is selectively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain,2017,121:2327-2334.
5 孙晓钰,杨瑞青,王保贵.中性粒细胞明胶酶相关脂质运载蛋白在慢性阻塞性肺疾病急性加重期的表达.临床肺科杂志,2017,22:679-682.
6 Bchir S,Nasr HB,Bouchet S,et al. Concomitant elevations of MMP-9,NGAL,pro MMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease. Journal of Cellular&Molecular Medicine,2017,21:1280-1291.
7 Global Initiative for Chronic Obstructive Lung Disease. GOLD 2017Global Strategy for the Diagnosis,Management and Prevention of COPD.
8 宣萱,李艳.降钙素原、超敏C反应蛋白、D-二聚体和纤维蛋白原在COPD急性加重期患者的动态变化及临床意义.临床和实验医学杂志,2015,14:202-204.
9 Lim JU,Lee JH,Ju SK,et al. Comparison of World Health Organization and Asia-Pacific body mass index classifications in COPD patients.International Journal of Chronic Obstructive Pulmonary Disease,2017,12:2465-2475.
10 胡国平,钟南山,冉丕鑫.中国的大气污染和COPD.中国胸心血管外科临床杂志,2016,23:107-112.
11 唐文芳,刘日辉,于雅琴,等. 2000-2014年中国40岁以上成人慢性阻塞性肺疾病患病率的Meta分析.吉林大学学报(医学版),2015,41:961-968.
12 Valacchi G,Maioli E,Sticozzi C,et al. Exploring the link between scavenger receptor B1 expression and chronic obstructive pulmonary disease pathogenesis. Annals of the New York Academy of Sciences,2015,1340:47-54.
13 Tse HN,Tseng CZS. Update on the pathological processes,molecular biology,and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease,2014,9:825-836.
14 官秋玥,向征.慢性阻塞性肺疾病中蛋白酶与抗蛋白酶系统的研究进展.国际呼吸杂志,2014,36:1185-1188.
15 高振,李风森,王晶,等.寒燥对慢性阻塞性肺疾病模型肺部蛋白酶-抗蛋白酶失衡的影响.中华中医药杂志,2014,29:3773-3777.
16 Sundar IK,Hwang JW,Wu S,et al. Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation. Biochemical&Biophysical Research Communications,2011,406:127-133.
17 Grzela K,Litwiniuk M,Zagorska W,et al. Airway remodeling in chronic obstructive pulmonary disease and asthma:the role of matrix metalloproteinase-9. Archivum Immunologiae Et Therapiae Experimentalis,2016,64:1-9.
18 张平,朱应群,李喆,等.维生素D与基质金属蛋白酶-9在慢性阻塞性肺疾病中的表达及相关性分析.国际呼吸杂志,2014,34:649-651.
19 Grzela K,Litwiniuk M,Zagorska W,et al. Airway remodeling in chronic obstructive pulmonary disease and asthma:the role of matrix metalloproteinase-9. Archivum Immunologiae Et Therapiae Experimentalis,2016,64:1-9.
20 Gilet A,Zou F,Boumenir M,et al. Aldosterone up-regulates MMP-9 and MMP-9/NGAL expression in human neutrophils through p38,ERK1/2and PI3K pathways. Experimental Cell Research,2014,331:152-63.
21 孙晓钰,杨瑞青,王保贵.中性粒细胞明胶酶相关脂质运载蛋白在慢性阻塞性肺疾病急性加重期的表达.临床肺科杂志,2017,22:679-682.
22 Vanessa A,Morena S,Javier C,et al. The potential of lipocalin-2/NGAL as biomarker for inflammatory and metabolic diseases:. Biomarkers:biochemical indicators of exposure,response,and susceptibility to chemicals,2015,20:565-571.