血清基质金属蛋白酶9在慢性阻塞性肺疾病吸烟患者高分辨CT不同表型中的表达及相关研究
发布时间：2018-08-24 07:30
【摘要】：目的:本研究旨在分析血清基质金属蛋白酶(matrix metalloprote inases,MMPs)-9在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)吸烟患者高分辨CT(high-resolution computed tomogra-phy,HRCT)不同表型中的水平变化及相关因素研究。方法:选取2016年1月-2017年1月于中国石油天然气集团中心医院呼吸内科入院COPD患者94例作为观察组。其中男性56例,女性38例;年龄分布为48-87岁,平均年龄(71.19±0.894)岁。并选取同时期我院体检中心体检者29例作为对照组。患者入组标准:(1)符合COPD诊断标准即符合中华医学会呼吸病学分会慢性阻塞性肺疾病学组制定的《慢性阻塞性肺疾病诊治指南(2013修订版)》:吸入支气管扩张剂后FEV1/FVC0.7,视为持续性气流受限,方可诊断为COPD;(2)年龄≥40岁;(3)患者及家属知情同意并签署知情同意书。对照组入组标准:(1)年龄≥40岁;(2)无吸烟史;(3)进行健康检查且显示肺功能正常、身体各机能指标均正常的健康人;(4)受试者知情同意并签署知情同意书。所有受试者排除标准:(1)不符合上述纳入标准者;(2)不愿参与本项研究者。所有入选者采集信息如下:性别、年龄、既往史、吸烟情况。观察组常规检查:血常规、血沉、PCT、CRP、肺功能、胸部HRCT等。将患者胸部HRCT进行图像处理与分析,根据患者肺气肿和支气管壁厚度严重程度,分为A、E、M三型;并根据患者吸烟情况将患者分为吸烟组和非吸烟组。使用北京冬歌生物科技有限公司提供MMP-9试剂盒,对所有受试者血清标本严格按照说明书进行MMP-9测定。应用SPSS 19.0软件进行数据分析。分析前对数据进行正态性及方差齐性检验。符合正态分布的计量资料采用x±s表示,非正态分布资料进行对数转换。组间正态分布的计量资料比较采用方差分析,多重比较采用LSD检验,组间非正态分布的计量资料采用秩和检验(Kruskal-Wallis H检验)。单因素相关分析采用Spearman相关分析法并逐个绘制散点图。计数资料比较采用Χ2检验,多因素相关性分析采用多元逐步线性回归分析。p0.05为差异有统计学意义。结果:1观察组与对照组mmp-9比较观察组mmp-9表达水平为(128.56±9.074ng/ml)明显高于健康对照组(27.23±10.213ng/ml)(p0.05),两者差异有统计学意义。2观察组中a、e、m三型mmp-9比较观察组中a型患者56例,mmp-9表达水平为(128.11±10.23ng/ml);e型患者10例,mmp-9表达水平为(132.06±6.78ng/ml);m型患者28例,mmp-9表达水平为(128.56±9.07ng/ml),三组两两比较差异无统计学意义。3在copd吸烟和非吸烟患者及其a、e、m三型中mmp-9的比较3.1吸烟组与非吸烟组mmp-9比较吸烟组患者mmp-9表达水平为(130.49±9.01ng/ml),非吸烟组患者mmp-9表达水平为(123.23±6.96ng/ml),且两组差异有统计学意义。3.2吸烟组a、e、m三型中mmp-9的比较吸烟组中m型患者mmp-9(128.31±7.77ng/ml)明显低于e、a型(133.69±10.17ng/ml)、(135.62±9.94ng/ml),差异有统计学意义(t=2.05,2.65,p0.05)。吸烟患者中mmp-9各表型间相比差异无统计学意义(p0.05)。4吸烟对患者ct分型相关分析4.1吸烟组与非吸烟组laa评分比较吸烟患者laa评分(9.38±4.62分)与非吸烟患者(6.32±4.45分)相比差异有统计学意义(t=2.86,p0.01)。4.2吸烟组与非吸烟组a、e、m三型中laa评分的比较吸烟患者和非吸烟患者中m型、e型的laa评分与a型相比差异均有统计学意义(p0.01),但m型与e型在laa评分上差异均没有统计学意义(p0.05)。4.3吸烟组与非吸烟组a、e、m三型中t/pa的比较吸烟组与非吸烟组t/pa相比差异无统计学意义(t=1.51,p0.05),但吸烟组和非吸烟组m型与a型t/pa相比差异有统计学意义(t=2.42,t=2.82,p0.05)。5炎性指标及肺功能比较5.1吸烟组与非吸烟组中性粒细胞百分数和淋巴细胞百分数之间比较吸烟组的外周血中性粒细胞百分数(76.78±10.80%)和淋巴细胞百分数(15.73±9.18%)与非吸烟组中性粒细胞百分数(67.41±12.65%)和淋巴细胞百分数(22.51±12.08%)相比差异有统计学意义(t=3.55,t=2.90,P0.01)。5.2吸烟组与非吸烟组FEV1%比较非吸烟患者FEV1%好于吸烟组,差异有统计学意义(t=2.11,P0.05)。6吸烟与COPD患者合并症数量对MMP-9的影响6.1合并症数量的影响合并症数量在3个以上的患者中,吸烟组和非吸烟组MMP-9差异有统计学意义(χ2=12.08,P0.01)。6.2合并症种类与MMP-9吸烟和非吸烟患者中合并心血管疾病MMP-9与没有合并心血管疾病患者相比,差异有统计学意义(P0.05)。结论:1观察组COPD患者血清MMP-9表达水平明显高于对照组,说明MMP-9参与COPD的发病机制。2COPD患者A、E、M不同表型MMP-9表达水平无明显差异,提示MMP-9并不是唯一参与气道壁增厚和肺气肿的金属蛋白酶。吸烟患者MMP-9表达水平更高,说明吸烟是造成气道炎症和气道结构破坏、气道重塑最重要的因素。吸烟组FEV1%下降更明显,说明吸烟导致更明显的气流受限。3吸烟患者外周血中性粒细胞百分比比非吸烟者更高,说明吸烟导致患者炎症反应更明显。4吸烟导致COPD患者中多种合并症有关,特别是心血管疾病。
[Abstract]:AIM: To analyze the changes of serum matrix metalloproteinase-9 (MMPs-9) levels in different phenotypes of high-resolution computed tomographic-phy (HRCT) in smokers with chronic obstructive pulmonary disease (COPD). From January to January 2017, 94 patients with COPD admitted to the Department of Respiratory Medicine, Central Hospital of China National Petroleum and Natural Gas Group were selected as the observation group, including 56 males and 38 females. The age distribution was 48-87 years with an average age of (71.19 (+ 0.894) years. Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (Revised Edition 2013): FEV1/FVC 0.7 after inhalation of bronchodilator, considered as persistent airflow limitation, can be diagnosed as COPD; (2) Age (> 40 years old); and (3) Informed consent and informed consent of patients and their families. The criteria for inclusion in the control group were: (1) age (> 40 years); (2) no history of smoking; (3) healthy persons with normal lung function and normal physical function; (4) informed consent and informed consent were signed by the subjects. (1) those who did not meet the inclusion criteria; (2) those who did not wish to participate in the study. The data were collected as follows: sex, age, past history, smoking status. Routine examination in observation group: blood routine, ESR, PCT, CRP, lung function, chest HRCT, etc. Group B and non-smoking group.MMP-9 kit provided by Beijing Dongge Biotechnology Co.Ltd was used to determine the serum MMP-9 in strict accordance with the specifications of all subjects.Data were analyzed by SPSS 19.0 software.The data were tested for normality and homogeneity of variance before analysis.The measurement data which accorded with normal distribution were expressed by x+s,but not by SPSS 19.0 software. Normal distribution data were logarithmically transformed. Variance analysis was used to compare the measurement data of normal distribution among groups, LSD test was used for multiple comparisons, Kruskal-Wallis H test was used for non-normal distribution among groups. Spearman correlation analysis was used for single factor correlation analysis and scatter plots were drawn one by one. _2 test, multivariate stepwise linear regression analysis was used for multivariate correlation analysis. The expression of MMP-9 was 128.11 (+ 10.23 ng / ml) in 56 patients with type a, 132.06 (+ 6.78 ng / ml) in 10 patients with type e, and 128.56 (+ 9.07 ng / ml) in 28 patients with type M. There was no significant difference between the three groups. Comparison 3.1 MMP-9 expression level in smoking group and non-smoking group was (130.49 [9.01 ng / ml], and that in non-smoking group was (123.23 [6.96 ng / ml], and there was significant difference between the two groups. 133.69 [10.17ng / ml], (135.62 [9.94ng / ml], the difference was statistically significant (t = 2.05, 2.65, p0.05). There was no significant difference between the MMP-9 phenotypes in smoking patients (p0.05). 4 Correlation analysis of CT typing between smoking and non-smoking patients The difference was statistically significant (t = 2.86, p0.01). 4.2 The LAA scores of smoking group and non-smoking group a, e, m were significantly different from those of smoking group and non-smoking group (p0.01), but there was no significant difference in the LAA scores of M and e between smoking group and non-smoking group (p0.05). There was no significant difference in t / PA between smoking group and non-smoking group (t = 1.51, p0.05), but there was significant difference in t / PA between smoking group and non-smoking group (t = 2.42, t = 2.82, p0.05). The percentage of peripheral blood neutrophils (76.78+10.80%) and the percentage of lymphocytes (15.73+9.18%) in the smoking group were significantly higher than those in the non-smoking group (67.41+12.65%) and the percentage of lymphocytes (22.51+12.08%) (t = 3.55, t = 2.90, P 0.01). Compared with non-smoking group, FEV1% was better than smoking group, the difference was statistically significant (t = 2.11, P 0.05). 6. The number of complications in smoking and COPD patients affected the number of MMP-9. The number of complications in more than three patients, smoking group and non-smoking group MMP-9 was significantly different (2 = 12.08, P 0.01). 6.2 complications and MMP-9 smoking type Conclusion: The expression level of MMP-9 in serum of COPD patients in observation group was significantly higher than that in control group, indicating that MMP-9 participated in the pathogenesis of COPD. MMP-9 is not the only metalloproteinase involved in airway wall thickening and emphysema. Smoking patients have higher levels of MMP-9 expression, suggesting that smoking is the most important factor causing airway inflammation, airway structural damage and airway remodeling. The percentage of granulocytes is higher than that of non-smokers, suggesting that smoking causes more pronounced inflammation. 4 Smoking causes a variety of complications in patients with COPD, especially cardiovascular disease.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R563.9
[Abstract]:AIM: To analyze the changes of serum matrix metalloproteinase-9 (MMPs-9) levels in different phenotypes of high-resolution computed tomographic-phy (HRCT) in smokers with chronic obstructive pulmonary disease (COPD). From January to January 2017, 94 patients with COPD admitted to the Department of Respiratory Medicine, Central Hospital of China National Petroleum and Natural Gas Group were selected as the observation group, including 56 males and 38 females. The age distribution was 48-87 years with an average age of (71.19 (+ 0.894) years. Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (Revised Edition 2013): FEV1/FVC 0.7 after inhalation of bronchodilator, considered as persistent airflow limitation, can be diagnosed as COPD; (2) Age (> 40 years old); and (3) Informed consent and informed consent of patients and their families. The criteria for inclusion in the control group were: (1) age (> 40 years); (2) no history of smoking; (3) healthy persons with normal lung function and normal physical function; (4) informed consent and informed consent were signed by the subjects. (1) those who did not meet the inclusion criteria; (2) those who did not wish to participate in the study. The data were collected as follows: sex, age, past history, smoking status. Routine examination in observation group: blood routine, ESR, PCT, CRP, lung function, chest HRCT, etc. Group B and non-smoking group.MMP-9 kit provided by Beijing Dongge Biotechnology Co.Ltd was used to determine the serum MMP-9 in strict accordance with the specifications of all subjects.Data were analyzed by SPSS 19.0 software.The data were tested for normality and homogeneity of variance before analysis.The measurement data which accorded with normal distribution were expressed by x+s,but not by SPSS 19.0 software. Normal distribution data were logarithmically transformed. Variance analysis was used to compare the measurement data of normal distribution among groups, LSD test was used for multiple comparisons, Kruskal-Wallis H test was used for non-normal distribution among groups. Spearman correlation analysis was used for single factor correlation analysis and scatter plots were drawn one by one. _2 test, multivariate stepwise linear regression analysis was used for multivariate correlation analysis. The expression of MMP-9 was 128.11 (+ 10.23 ng / ml) in 56 patients with type a, 132.06 (+ 6.78 ng / ml) in 10 patients with type e, and 128.56 (+ 9.07 ng / ml) in 28 patients with type M. There was no significant difference between the three groups. Comparison 3.1 MMP-9 expression level in smoking group and non-smoking group was (130.49 [9.01 ng / ml], and that in non-smoking group was (123.23 [6.96 ng / ml], and there was significant difference between the two groups. 133.69 [10.17ng / ml], (135.62 [9.94ng / ml], the difference was statistically significant (t = 2.05, 2.65, p0.05). There was no significant difference between the MMP-9 phenotypes in smoking patients (p0.05). 4 Correlation analysis of CT typing between smoking and non-smoking patients The difference was statistically significant (t = 2.86, p0.01). 4.2 The LAA scores of smoking group and non-smoking group a, e, m were significantly different from those of smoking group and non-smoking group (p0.01), but there was no significant difference in the LAA scores of M and e between smoking group and non-smoking group (p0.05). There was no significant difference in t / PA between smoking group and non-smoking group (t = 1.51, p0.05), but there was significant difference in t / PA between smoking group and non-smoking group (t = 2.42, t = 2.82, p0.05). The percentage of peripheral blood neutrophils (76.78+10.80%) and the percentage of lymphocytes (15.73+9.18%) in the smoking group were significantly higher than those in the non-smoking group (67.41+12.65%) and the percentage of lymphocytes (22.51+12.08%) (t = 3.55, t = 2.90, P 0.01). Compared with non-smoking group, FEV1% was better than smoking group, the difference was statistically significant (t = 2.11, P 0.05). 6. The number of complications in smoking and COPD patients affected the number of MMP-9. The number of complications in more than three patients, smoking group and non-smoking group MMP-9 was significantly different (2 = 12.08, P 0.01). 6.2 complications and MMP-9 smoking type Conclusion: The expression level of MMP-9 in serum of COPD patients in observation group was significantly higher than that in control group, indicating that MMP-9 participated in the pathogenesis of COPD. MMP-9 is not the only metalloproteinase involved in airway wall thickening and emphysema. Smoking patients have higher levels of MMP-9 expression, suggesting that smoking is the most important factor causing airway inflammation, airway structural damage and airway remodeling. The percentage of granulocytes is higher than that of non-smokers, suggesting that smoking causes more pronounced inflammation. 4 Smoking causes a variety of complications in patients with COPD, especially cardiovascular disease.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R563.9
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