引用本文:李 果,陈小兵,李 刚,梁晓彤,陶 维,陈绍平.中性粒细胞明胶酶相关脂质运载蛋白与基质金属蛋白酶9在不同时期COPD患者外周血中的表达变化及意义[J].中国临床新医学,2021,14(7):685-690.
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中性粒细胞明胶酶相关脂质运载蛋白与基质金属蛋白酶9在不同时期COPD患者外周血中的表达变化及意义
李 果,陈小兵,李 刚,梁晓彤,陶 维,陈绍平
637200 四川,西充县人民医院呼吸与危重症医学科(李 果);637000 南充,川北医学院附属医院呼吸与危重症医学科(陈小兵,陶 维,陈绍平);638400 四川,武胜县人民医院老年医学科(李 刚);637100 四川,南充市第五人民医院呼吸内科(梁晓彤)
摘要:
[摘要] 目的 探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、基质金属蛋白酶9(MMP-9)基因在不同时期慢性阻塞性肺疾病(COPD)患者外周血单个核细胞中的表达变化并分析其临床意义。方法 前瞻性纳入2016年11月至2017年7月COPD急性加重期(AECOPD)组患者25例、稳定期COPD(SCOPD)组患者80例和体检正常者(对照组)40名,并根据上一年急性加重次数(或住院次数)将SCOPD组患者分为低风险组39例和高风险组41例。所有受试者于清晨空腹采集外周静脉血标本,在分离和提取单个核细胞后,采用实时荧光定量PCR技术检测并比较各组NGAL mRNA、MMP-9 mRNA基因的表达差异。同时分析两者间的关系及其与体质量指数、吸烟指数、血常规和肺功能等临床指标间的相关性。结果 (1)AECOPD组NGAL mRNA和MMP-9 mRNA基因相对表达量高于SCOPD组和对照组,且SCOPD组高于对照组,差异均有统计学意义(P均<0.01)。(2)SCOPD患者高风险组NGAL mRNA和MMP-9 mRNA基因相对表达量均高于低风险组,差异有统计学意义(P均<0.05)。(3)AECOPD组和SCOPD组NGAL mRNA和MMP-9 mRNA基因相对表达量间均呈显著正相关(r=0.831,P<0.01;r=0.764,P<0.01)。(4)SCOPD组NGAL mRNA、MMP-9 mRNA基因相对表达量与肺功能FEV1%pred均呈负相关(r=-0.416,P<0.01;r=-0.312,P<0.05)。(5)SCOPD组NGAL mRNA和MMP-9 mRNA基因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呈正相关(P均<0.05),与体质量指数、吸烟指数、FEV1/FVC等临床指标无明显相关性(P均>0.05)。结论 NGAL和MMP-9可能共同参与了COPD的发生与发展,其基因相对表达量或可成为评估COPD病情严重程度的新指标。
关键词:  中性粒细胞明胶酶相关脂质运载蛋白  基质金属蛋白酶9  慢性阻塞性肺疾病  外周血  基因  相对表达量
DOI:10.3969/j.issn.1674-3806.2021.07.10
分类号:R 563.3
基金项目:
Expression changes of neutrophil gelatinase-associated lipocalin and matrix metalloproteinase-9 in peripheral blood of patients with COPD at different stages and their significances
LI Guo, CHEN Xiao-bing, LI Gang, et al.
Department of Respiratory and Critical Care Medicine, Xichong County People′s Hospital, Sichuan 637200, China
Abstract:
[Abstract] Objective To investigate the expression changes of neutrophil gelatinase-associated lipocalin(NGAL) and matrix metalloproteinase-9(MMP-9) genes in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease(COPD) at different stages and to analyze their clinical significances. Methods From November 2016 to July 2017, twenty-five patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD), 80 patients with stable chronic obstructive pulmonary disease(SCOPD) and 40 healthy subjects were prospectively enrolled into the AECOPD group, the SCOPD group and the control group, respectively. According to the frequency of acute exacerbation episode(or the frequency of hospitalization) in the previous year, the patients of the SCOPD group were divided into a low-risk group(n=39) and a high-risk group(n=41). The fasting peripheral venous blood samples were collected from all the subjects in the early morning. After mononuclear cells were isolated and extracted, real-time quantitative polymerase chain reaction(RT-qPCR) technology was used to detect the expressions of NGAL mRNA and MMP-9 mRNA genes in each group and the differences in the gene expressions of NGAL mRNA and MMP-9 mRNA were compared among all the groups. At the same time, the relationship between NGAL mRNA and MMP-9 mRNA gene expressions and their correlations with clinical indicators such as Body Mass Index, Smoking Index, blood routine and lung function were analyzed. Results (1)The relative expression levels of NGAL mRNA and MMP-9 mRNA genes in the AECOPD group were higher than those in the SCOPD group and the control group, and the relative expression levels of NGAL mRNA and MMP-9 mRNA genes in the SCOPD group were higher than those in the control group, and the differences were statistically significant(P<0.01). (2)The relative expression levels of NGAL mRNA and MMP-9 mRNA genes in the high-risk group were higher than those in the low-risk group, and the differences were statistically significant(P<0.05). (3)The relative expression levels of NGAL mRNA and MMP-9 mRNA genes in the AECOPD group and the SCOPD group were significantly positively correlated, and the correlations were statistically significant(r=0.831, P<0.01; r=0.764, P<0.01). (4)The relative expression levels of NGAL mRNA and MMP-9 mRNA genes in the SCOPD group were negatively correlated with the forced expiratory volume in one second/prediction(FEV1%pred), and the correlations were statistically significant(r=-0.416, P<0.01; r=-0.312, P<0.05). (5)The relative expression levels of NGAL mRNA and MMP-9 mRNA genes in the SCOPD group were positively correlated with the total number of peripheral blood white blood cells, the total number of neutrophils and the percentage of neutrophils, and the correlations were statistically significant(P<0.05). The relative expression levels of these genes had no significant correlation with such clinical indexes as Body Mass Index, Smoking Index and forced expiratory volume in one second/forced vital capacity(FEV1/FVC)(P>0.05). Conclusion NGAL and MMP-9 may be involved in the occurrence and development of COPD, and their relative gene expression levels may become new indicators for evaluating the severity of COPD.
Key words:  Neutrophil gelatinase-associated lipocalin(NGAL)  Matrix metalloproteinase-9(MMP-9)  Chronic obstructive pulmonary disease(COPD)  Peripheral blood  Gene  Relative expression