Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis

Introduction

Matrix metalloproteinases (MMPs) play a role in infectious diseases through extracellular matrix (ECM) degradation, which favors the migration of immune cells from the bloodstream to sites of inflammation. Although higher levels of MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) have been found in small series of patients with sepsis, MMP-10 levels have not been studied in this setting. The objective of this study was to determine the predictive value of MMP-9, MMP-10, and TIMP-1 on clinical severity and mortality in a large series of patients with severe sepsis.

Methods

This was a multicenter, observational, and prospective study carried out in six Spanish Intensive Care Units. We included 192 (125 surviving and 67 nonsurviving) patients with severe sepsis and 50 age- and sex-matched healthy controls in the study. Serum levels of MMP-9, MMP-10, TIMP-1, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 were measured in patients with severe sepsis at the time of diagnosis and in healthy controls.

Results

Sepsis patients had higher levels of MMP-10 and TIMP-1, higher MMP-10/TIMP-1 ratios, and lower MMP-9/TIMP-1 ratios than did healthy controls (P < 0.001). An association was found between MMP-9, MMP-10, TIMP-1, and MMP-9/TIMP-1 ratios and parameters of sepsis severity, assessed by the SOFA score, the APACHE-II score, lactic acid, platelet count, and markers of coagulopathy. Nonsurviving sepsis patients had lower levels of MMP-9 (P = 0.037), higher levels of TIMP-1 (P < 0.001), lower MMP-9/TIMP-1 ratio (P = 0.003), higher levels of IL-10 (P < 0.001), and lower TNF-α/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-α and IL-10 levels. The risk of death in sepsis patients with TIMP-1 values greater than 531 ng/ml was 80% higher than that in patients with lower values (RR = 1.80; 95% CI = 1.13 to 2.87;P = 0.01; sensitivity = 0.73; specificity = 0.45).

Conclusions

The novel findings of our study on patients with severe sepsis (to our knowledge, the largest series reporting data about MMP levels in sepsis) are that reduced MMP-9/TIMP-1 ratios and increased MMP-10 levels may be of great pathophysiologic significance in terms of severity and mortality, and that TIMP-1 levels may represent a biomarker to predict the clinical outcome of patients with sepsis.     

Diagnostic value of serum neutrophil gelatinase-associated lipocalin,interleukin-6 and anti-citrullinated alpha-enolase peptide 1 for lower respiratory tract infections

ObjectivesThe aim of this study was to explore the auxiliary diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) and anti-citrullinated alpha-enolase peptide 1 (CEP-1) in lower respiratory tract infections (LRTIs).MethodsBlood samples were collected from 99 in-patients with LRTIs [62 community-acquired pneumonia (CAP), 14 acute exacerbated chronic obstructive pulmonary diseases (AECOPD), 23 other diseases] and 50 healthy subjects. NGAL, CEP-1 and IL-6 were measured and compared. IL-6 was tested by electrochemiluminescence assay kit on Roche E601 immunology analyzer, CEP-1 was assessed with enzyme-linked immunosorbent assay kit, and NGAL was detected by latex immunoturbidimetric assay kit on Beckman Coulter AU2700.ResultsCompared with healthy controls, NGAL and IL-6 levels were significantly increased in the patients with LRTIs, the area under the curves (AUC) was 0.97 and 0.88 respectively (P < 0.01). The sensitivity and specificity of NGAL at a cut-off of 86 ng/ml were 93.0% and 96.0%, respectively, in which the sensitivity was consistent with IL-6 (P = 0.21) and the specificity was better than IL-6 (P < 0.01). CEP-1 slightly increases in the patient group, however the difference was not significant (P = 0.41). The levels of NGAL and IL-6 was no differences in different diseases, the P-value was 0.50 and 0.29, respectively. LRTIs with and without underlying diseases have similar NGAL and IL-6 values.ConclusionsNGAL, rather than CEP-1, may be appealing adjuncts for diagnosis of LRTIs. NGAL proved to be a better biomarker than IL-6.     

中性粒细胞明胶酶相关脂质运载蛋白在重症肺炎合并脓毒症患儿中的表达及临床价值

目的探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在重症肺炎合并脓毒症患儿中的表达及临床价值。方法选取该院106例重症肺炎合并脓毒症患儿,根据严重程度分为脓毒症组、严重脓毒症组和脓毒症休克组,根据出院时转归分为预后良好组和预后不良组,根据是否合并肾功能障碍分为肾功能障碍组和无肾功能障碍组。分析患儿的NGAL、降钙素原(PCT)、白细胞介素-6(IL-6)、C-反应蛋白(CRP)及小儿危重病例评分(PCIS),采用Spearman秩相关及受试者工作特征曲线(ROC曲线)对各指标进行分析与评价。结果肾功能障碍组NGAL水平明显高于无肾功能障碍组,两组比较差异有统计学意义(P<0.05);NGAL、CRP、PCT、IL-6水平和PCIS在脓毒症组、严重脓毒症组和脓毒症休克组中的差异均有统计学意义(均P<0.05),其中NGAL、PCT、IL-6水平在3组中依次升高,PCIS在3组中依次降低,组间两两比较差异均有统计学意义(均P<0.05);与预后良好组比较,预后不良组的NGAL、CRP、PCT、IL-6水平明显升高,PCIS明显降低,差异均有统计学意义(均P<0.05);Spearman相关分析显示NGAL与CRP、PCT、IL-6呈正相关,与PCIS呈负相关(均P<0.05);NGAL用于预测预后不良的曲线下面积(AUC)为0.915,仅次于PCIS的0.949。结论NGAL在重症肺炎合并脓毒症患儿病情严重程度及预后预测中可能具有一定的临床价值。     

尿肝型脂肪酸结合蛋白和尿中性粒细胞明胶酶相关脂质运载蛋白用于诊断严重脓毒症患者急性肾损伤

目的：探讨尿肝型脂肪酸结合蛋白(uL-FABP)及其与尿中性粒细胞明胶酶相关脂质运载蛋白(u-NGAL)在判断严重脓毒症患者是否发生急性肾损伤(AKI)及评估 AKI 严重程度中的价值,以期能为 AKI 的早期诊断提供方便可靠的方法。方法前瞻性收集严重脓毒症和脓毒症休克患者入院时、入院后12小时、24小时、48小时和72小时的尿标本,分别检测血清肌酐(SCr)、uL-FABP 和 u-NGAL 水平,比较 AKI 和非 AKI 患者各标志物的动态变化情况。运用受试者工作特征(ROC)曲线及曲线下面积(AUC),评估标志物单独及联合应用时诊断 AKI 的准确性。结果总共60例患者中26例(43.3%)发生了 AKI,与非 AKI 患者相比较,AKI 患者的 uL-FABP 和 u-NGAL 水平显著升高。uL-FABP 和 u-NGAL 水平在 AKI 组入院后12小时即显著高于非 AKI 组,其浓度变化明显早于 SCr。在入院后12小时,uL-FA BP 和 u-NGAL 的 AUC 分别为0.901和0.906,在界值分别为985μg/g·Cr 和52μg/g·Cr时,uL-FABP 和 u-NGAL 的敏感度和特异度分别为85.2%和84.6%以及87.8%和86.5%。结论 uL-FABP 和 u-NGAL 在严重脓毒症患者 AKI 早期即显著升高,比 SCr 能更早地预测 AKI 的发生和严重程度,两者联合应用则可使诊断的精确性进一步提高。     

Clinical assessment of neutrophil gelatinase-associated lipocalin as a potential diagnostic marker for neonatal sepsis: a prospective cohort study

Sepsis is a life-threatening condition associated with high morbidity and mortality rates among neonates. Clinical diagnosis is limited due to the neonates’ unspecific signs and symptoms as well as the long time required to obtain the blood culture results. Consequently, there is an urgent need for new biomarkers to early diagnose neonatal sepsis. We aimed to evaluate Neutrophil Gelatinase-Associated Lipocalin (NGAL) diagnostic performance to detect neonatal sepsis. We enrolled 30 neonates with sepsis admitted to the neonatal intensive care units and 30 age- and sex-matched healthy neonates recruited from the neonatal outpatient clinic during their routine follow-up visits. We measured NGAL levels by sandwich enzyme-linked immunosorbent assay, the C-reactive protein (CRP) with nephelometry technique using BN II nephelometer, and the complete blood count by Mindray BC-6800 analysers. NGAL, CRP, TLC, haemoglobin, and platelet levels showed significant differences between cases and control (all p < .001). Of the 30 neonates with sepsis, 17 neonates (56.7%) survived. At 0 h, the NGAL level showed no statistically significant difference between the non-survivors and survivors’ groups; however, after 96 h, NGAL was significantly higher in the non-survivors group (p ˂ .001). Our diagnostic analysis showed that NGAL levels have strong discrimination power to early differentiate neonates with sepsis; at the 475.00 pg/ml cut-off value, NGAL showed both sensitivity and specificity of 100% with an area under curve of 100%. Conclusion: Our study suggests that NGAL could be a promising biomarker for neonatal sepsis detection. Further studies with larger sample sizes and survival analysis are warranted to confirm this finding and to clarify the efficacy of NGAL in survival prediction.

Key findings

• NGAL level was high in neonates with sepsis
• NGAL level was high in non-survived neonates
• NGAL could be a promising diagnostic marker for sepsis

     

MMP-1、TIMP-1和U-PA在血管成形术后再狭窄中表达的实验研究

目的：本实验以兔髂动脉为模型，探讨基质金属蛋白酶－1（MMP－1），基质金属蛋白酶－1组织抑制剂（TIMP－1）和尿激酶纤溶酶原激活剂（U－PA）在血管成形术后再狭窄中的作用。方法：对48只家兔髂动脉粥样硬化模型血管进行球囊扩张术，分别于术后不同时间行血管造影后处死动物，取扩张血管段用病理方法观察血管形态，用原位杂交法测定MMP－1，TIMP－1和U－PA的mRNA表达，结果：球囊扩张术后各时间点MMP－1和TIMP－1 mRNA始终处于弱表达，没有明显升高；球囊扩张术后1d,U-PA mRNA在内膜和中膜表达增加（＋＋），4d时达高峰（＋＋＋），7d后开始下降并保持弱表达（＋），结论：MMP－1，TIMP－1和U－PA在血管成形术后异常表达，为新生内膜形成的重要原因，可能在成形术后再狭窄中起重要作用。     

基质金属蛋白酶-9及其组织抑制物-1在妊娠期糖尿病患者胎盘组织中的表达及其意义

目的：探讨妊娠期糖尿病患者胎盘组织基质金属蛋白酶-9（MMP9）及其组织抑制物-1（TIMPl）mRNA的表达和意义。方法：收集28例妊娠期糖尿病患者胎盘组织，采用原位杂交法从RNA水平检测其MMP9和TIMP1的表达．同时收集18例正常足月妊娠的胎盘组织进行对照。结果：正常妊娠时MMP9和TIMP1 mRNA在胎盘绒毛中呈强阳性表达，而妊娠期糖尿病患者其胎盘绒毛中MMP9和TIMP1 mRNA表达减弱，差异有显著性（P〈0．05）．其MMP9／TIMP1比值显著小于正常妊娠时的比值，两者比较差异有显著性（P〈0．05）。结论：妊娠期糖尿病患者，尤其合并重度子痫前期的患者，其胎盘绒毛中MMP9和TIMP1 mRNA表达均减少，提示妊娠期糖尿病患者存在着胎盘血管重铸异常，易引起胎盘血流灌注不良。     

口腔疣状癌基质金属蛋白酶-2、基质金属蛋白酶-9和金属蛋白酶组织抑制因子-2的表达及其相关性的研究

目的:研究口腔疣状癌中基质金属蛋白酶(MMP)-2、MMP-9及金属蛋白酶组织抑制因子(TIMP-2)的表达.探讨其在口腔疣状癌发生发展过程中的作用和意义.方法:取25例口腔疣状癌,10例正常口腔黏膜,25例口腔鳞癌(高、低分化鳞癌各为15、10例),应用免疫组织化学法检测上述标本中MMP-2、MMP-9及,TIMP-2的表达和分布.结果:正常口腔黏膜组织TIMP-2为阴性表达:MMP-2、MMP-9的阳性表达率分别为10.00%、20.00%.口腔疣状癌MMP-2阳性表达率为28.00%.MMP-9阳性表达率为44.00%,TIMP-2阳性表达率为72.00%.口腔疣状癌、口腔高分化鳞癌、口腔低分化鳞癌MMP-2、MMP-9、TIMP-2表达均高于正常口腔黏膜(P<0.05).结论:在口腔疣状癌,口腔高分化鳞癌、口腔低分化鳞癌中.MMP-2与MMP-9的阳性表达率呈正相关,与TIMP-2呈负相关;相关分析发现,MMP-2、MMP-9和TIMP-2的袁达两两相关,同时3者的表达可能单独或共同参与.     

基质金属蛋白酶2,9及其抑制剂3在脑梗死中的作用

目的通过注入自体血栓形成大鼠脑梗死模型,研究其不同时段基质金属蛋白酶（matrix metalloproteinase,MMP）2、9和基质金属蛋白酶抑制剂（tissue inhibitor metalloproteinase,TIMP）3的表达规律。方法66只成年Sprague Dawley大鼠随机分为3组,空白对照组（6只）、假手术对照组（30只）和手术实验组（30只）。实验组给予自体血栓经颈内动脉注入制备大鼠脑梗死标本;假手术对照组做同样处理,但不给予血栓注入干预,于术后24h,48h,3d,5d,7d麻醉并灌注固定取脑。观察大鼠行为学改变;采用免疫组化方法检测标本MMP-2,MMP-9,TIMP-3表达,了解其与病变之间关系。结果实验组大鼠行为学改变较其他组明显;HE染色下,组织病理变化明显;免疫组化染色显示MMP-2,MMP-9,TIMP-3表达均较其他两组增高,统计学结果显著性差异（P〈0．05）。结论MMP-2和MMP-9在脑梗死中与疾病损伤相关,TIMP-3有对抗作用。     

NGAL基因克隆载体的构建与鉴定

目的构建中性粒细胞明胶酶相关脂质运载蛋白 （neutrophil gelatinase - associated lipocalin, NGAL） 基因克隆载体。方法RT—PCR扩增宫颈癌Hela细胞NGAL cDNA片断,将纯化后PCR产物插入pGEM—T载体,构建重组质粒,重组子通过琼脂糖电泳、特异性内切酶切割及测序予以鉴定。结果成功构建了NGAL基因克隆载体2个。结论为NGAL基因的定量检测提供了基本实验条件。     

NGAL基因克隆载体的构建与鉴定

目的 构建中性粒细胞明胶酶相关脂质运载蛋(neutrophil gelatinase-associated lipocalin,NGAL)基因克隆载体.方法 RT-PCR扩增宫颈癌Hela细胞NGAL cDNA片断,将纯化后PCR产物插入pGEM-T载体,构建重组质粒,重组子通过琼脂糖电泳、特异性内切酶切割及测序予以鉴定.结果 成功构建了NGAL基因克隆载体2个.结论 为NGAL基因的定量检测提供了基本实验条件.     

尿肾损伤分子1和中性粒细胞明胶酶相关脂质运载蛋白对脓毒症合并急性肾损伤患者早期连续性肾脏替代治疗的预测价值

目的探讨尿肾损伤分子1（KIM-1）及中性粒细胞明胶酶相关脂质运载蛋白（NGAL）对脓毒症合并急性肾损伤（AKI）患者早期连续性肾脏替代治疗（CRRT）的预测价值。 方法选择温州市人民医院2012年7月至2015年11月收治的脓毒症合并AKI的患者159例,根据是否CRRT治疗,分为非CRRT组（92例）及CRRT组（67例）。收集所有患者尿液标本,采用酶联免疫吸附测定法检测尿KIM-1及NGAL水平。对两组患者的一般资料进行比较,并采用Logistic回归分析影响脓毒症合并AKI患者早期CRRT治疗的相关因素。同时通过受试者工作特征曲线（ROC）评价尿KIM-1、NGAL浓度在预测脓毒症AKI患者需CRRT的价值。 结果非CRRT组及CRRT组患者在年龄[（65 ± 18）岁vs.（77 ± 11）岁,t=26.380,P<0.001]、腹腔感染[8/92 vs. 23/67,χ²=16.228,P<0.001]、四肢皮肤软组织感染[19/92 vs. 2/67,χ²=10.556,P<0.001]、冠心病[46/92 vs. 50/67,χ²=9.828,P=0.002]、糖尿病[24/92 vs. 38/67,χ²=15.289,P<0.001]、慢性心功能不全[36/92 vs. 52/67,χ²=23.229,P<0.001]、气管插管留置>48 h [32/92 vs. 35/67,χ²=5.239,P=0.024]、急性病生理学和长期健康评价（APACHE）Ⅱ评分[（16 ± 6）分vs.（22 ± 5）分,t=40.671,P<0.001]、尿KIM-1 [（17 ± 4）ng·L^-1·Cr^-1 vs.（29 ± 19）ng·L^-1·Cr^-1,t=34.849,P<0.001]及NGAL水平[（5.7 ± 1.4）ng·L^-1·Cr^-1 vs.（7.7 ± 1.6）ng·L^-1·Cr^-1,t=65.483,P<0.001]的比较差异均有统计学意义。Logistic回归分析统计结果显示：糖尿病、慢性心功能不全、APACHEⅡ评分>18分、尿KIM-1浓度>21.0 ng·L^-1·Cr^-1及NGAL浓度>6.5 ng·L^-1·Cr^-1是影响脓毒症AKI患者选择CRRT治疗的相关因素;尿KIM-1、NGAL水平及两者联合预测患者需CRRT治疗的ROC曲线下面积分别为：0.783（95%CI：0.702~0.864,P<0.05）、0.819（95%CI：0.753~0.886,P<0.05）及0.867（95%CI：0.810~0.923,P<0.05）;NGAL及KIM-1的约登指数分别为0.465和0.502,两者联合后,约登指数为0.603。 结论尿KIM-1及NGAL水平对早期预测脓毒症合并AKI患者介入CRRT治疗有一定的应用价值,且两者联合检测更具有预测价值。     

基质金属蛋白酶-9及组织抑制因子-1在老年犬持续性心房颤动心房组织中表达

目的探讨基质金属蛋白酶（matrixmetalloproteinase,MMP）-9及组织抑制因子（tissueinhibitorsofmetalloproteinase,TIMP）-1在老年犬持续性心房颤动（房颤）心房肌组织中表达变化及其与心房颤动及纤维化发生的关系。方法健康比格犬18只随机分为成年、老年窦性心律组各5只、成年、老年持续性房颤组各4只。采用Masson三色法染色,计算胶原容积分数以测定纤维化程度,采用RT-PCR检测左心房MMP-9及TIMP-1的mRNA水平表达情况,采用蛋白质印迹法测定其蛋白水平表达情况。结果与成年窦性心律组比较,其余3组心房肌组织纤维化程度明显增高（P〈0．01）;TIMP-1mRNA表达水平下降（P〈0．05）,MMP-9蛋白表达水平升高（P〈0．01）,TIMP-1蛋白表达水平下降（P％0．01）;老年窦性心律组及老年持续性房颤组MMP-9mRNA表达水平较成年窦性心率组升高（P〈0．05）;与成年持续性房颤组比较,老年持续性房颤组纤维化程度增加,胶原容积分数明显增高（P％0．05）,TIMP-l蛋白表达水平下降（P〈0．01）。结论心房组织中MMP9和TIMP1基因表达失衡可能是影响胶原代谢、造成增龄性心房颤动时心房肌纤维化的分子机制之一,与增龄性心房颤动的发生和持续有关。     

Clinical review: Predictive value of neutrophil gelatinase-associated lipocalin for acute kidney injury in intensive care patients

Neutrophil gelatinase-associated lipocalin (NGAL) may be an early marker of acute kidney injury (AKI), but elevated NGAL occurs in a wide range of systemic diseases. Because intensive care patients have high levels of comorbidity, our objective was to conduct a systematic review of the literature to evaluate the value of plasma and urinary NGAL to predict AKI in these patients. We conducted a systematic electronic literature search of MEDLINE through PubMed, EMBASE, and Cochrane Library for all English language research publications evaluating the predictive value of plasma or urinary NGAL (or both) for AKI in adult intensive care patients. Two authors independently extracted data by using a standardized extraction sheet including study characteristics, type of NGAL measurements, and type of outcome measures. The primary summary measure was area under receiver operating characteristic curve (AuROC) for NGAL to predict study outcomes. Eleven studies with a total of 2,875 (range of 20 to 632) participants were included: seven studies assessed urinary NGAL and six assessed plasma NGAL. The included studies varied in design, including observation period from NGAL sampling to AKI follow-up (range of 12 hours to 7 days), definition of baseline creatinine value, and urinary NGAL quantification method (normalizing to urinary creatinine or absolute concentration). AuROC values for the prediction of AKI ranged from 0.54 to 0.98. Five studies reported AuROC for use of renal replacement therapy ranging from 0.73 to 0.89, and four studies reported AuROC for mortality ranging from 0.58 to 0.83. There were no differences in the predictive values of urinary and plasma NGAL. The heterogeneity in study design and results made it difficult to evaluate the value of NGAL to predict AKI in intensive care patients. NGAL seems to have reasonable value in predicting use of renal replacement therapy but not mortality.     

MMP-9和TIMP-1在不明原因不孕症患者子宫内膜的表达

目的检测基质金属蛋白酶-9（MMP-9）和组织金属蛋白酶抑制物-1（TIMP-1）在不明原因不孕症子宫内膜和正常子宫内膜中的表达,探讨两者与不明原因不孕的关系。方法应用免疫组化SP法,检测MMP-9和TIMP-1在20例不孕症患者的种植窗期子宫内膜和20例正常子宫内膜中的表达。结果MMP-9／TIMP-1在2组子宫内膜的腺上皮细胞和基质细胞的胞浆中均有不同程度的表达。MMP-9／TIMP-1在正常子宫内膜中呈高表达状态;在不孕子宫内膜表达较低,与正常子宫内膜组织相比差异有统计学意义（P〈0．05）。结论不明原因不孕症妇女子宫内膜种植窗期MMP-9和TIMP-1的低表达,可能是导致不明原因不孕症的重要因素之一。     

MMP-9和TIMP-1在不明原因不孕症患者子宫内膜的表达

Objective To study the expression situation of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the endometrium of women with unexplained infertility and normal endometrium, and to explore the relationship between MMP-9/TIMP-1 expres-sion and unexplained infertility. Methods Immunohistochemieal assay(SP method) was employed to deteet the expression of MMP-9/TIMP-1 in 20 cases of impaired endometrium(unexplained infertility group,endometrial plantation window phase)and 20 cases of normal endometrium(heahhy control group). Results There were different levels of MMP-9/TIMP-1 expression in kytoplasms of glandular epicytes and stromal cells of all endometrial samples. The expression of MMP-9/TIMP-1 was signifi-cantly weaker in unexplained infertility group than that in healthy control group(P＜0.05). Conclusion Low expression of MMP-9/TIMP-1 in the endometrial plantation window phase may be one of impor-tant factors for unexplained infertility.     

基质金属蛋白酶-9及组织抑制剂-1在大鼠肠粘连形成过程中的作用

目的:探讨基质金属蛋白酶-9(MMP-9)及组织抑制剂-1(TIMP-1)在术后肠粘连形成过程中的表达变化及其意义。方法:用干纱布擦伤回肠浆膜,制成大鼠肠粘连模型,采用免疫组化和图像分析方法,与对照组比较,观察术后2、7、14d时粘连肠组织中MMP-9及TIMP-1的表达变化。结果:与对照组比较,术后2d时模型组织中MMP-9的表达显著增加(P<0.05),而术后7、14d时粘连组织中MMP-9的表达较对照组均显著减少(P<0.01);术后各时相点时粘连肠组织中TIMP-1的表达均显著高于对照组(均P<0.05)。结论:MMP-9及TIMP-1在术后肠粘连的形成过程中发挥着重要的作用。     

慢性阻塞性肺疾病患者急性加重期血清基质金属蛋白酶抑制剂及基质金属蛋白酶9浓度与肺功能变化的关系

目的探讨慢性阻塞性肺疾病急性加重期(AECOPD)患者血清MMP-9、TIMP-1浓度的变化及其与肺功能变化的关系。方法应用酶联免疫吸附(ELISA)方法检测58例AECOPD患者和30名健康人血清中MMP-9、TIMP-1浓度。结果AECOPD患者血清MMP-9、TIMP-1浓度[(128.89±115.84)ng/mL、(228.28±107.133)ng/mL]明显高于对照组[(30.65±18.43)ng/mL、(133.69±41.41)ng/mL,P<0.01]。AECOPD组和对照组血清MMP-9、TIMP-1浓度与FEV1占预计值%具有负相关性(r=-0.591、-0.651,P<0.01);AECOPD组和对照组血清MMP-9、TIMP-1浓度与FEV1/FVC%具有负相关性(r=-0.558、-0.653,P<0.01);MMP-9/TIMP-1比率与FEV1占预计值%及FEV1/FVC%具有负相关性(r=-0.373、-0.356,P<0.05)。结论MMP-9、TIMP-1是引起肺功能下降很重要的因素。