冠心病基质金属蛋白酶-9及抑制物与血管紧张素Ⅱ的血清浓度

目的观察不同类型冠心病病人血清基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、组织基质金属蛋白酶抑制物-1(tissue-inhibitor of metalloproteinase-1,TIMP-1)和血管紧张素Ⅱ(anginotensinⅡ, AngⅡ)的血清浓度及相关关系,探讨急性冠状动脉综合征发病机制。方法冠心病病人分为急性心肌梗死组、不稳定心绞痛组(上述两组合称急性冠状动脉综合征组)和稳定心绞痛组,每组病人30例,另设健康对照组30例,比较各组间血清MMP-9、TIMP-1、MMP-9／TIMP-1和AngⅡ水平。结果急性心肌梗死组和不稳定心绞痛组血清MMP-9、MMP-9／TIMP-1和AngⅡ水平高于对照组,差异有统计学意义(P<0．01),但稳定心绞痛组血清MMP-9、TIMP-1、MMP-9／TIMP-1和AngⅡ水平与对照组比较差异无统计学意义(P> 0．05),急性冠状动脉综合征组病人血清MMP-9、MMP-9／TIMP-1与AngⅡ水平呈正相关(P<0．01)。结论血清MMP-9、MMP-9／TIMP-1和AngⅡ水平的增高与急性冠状动脉综合征相关,可作为评价冠状动脉粥样硬化斑块稳定性与病变严重程度的一个参考指标。     

急性冠脉综合征患者炎性标记物与斑块稳定性的研究

目的 观察急性冠脉综合征(ACS)患者炎性标记物与斑块稳定性的关系.方法 时40例ACS患者和35例稳定型心绞痛(SA)患者测定血清高敏C反应蛋白(hs-CRP)、基质金属蛋白酶-9(MMP-9)、组织型基质金属蛋白酶抑制剂-1(TIMP-1)的含量,分析与冠状动脉造影狭窄程度积分之间的关系.结果 ACS组血清hs-CRP、MMP-9含量均高于DA组(P<0.05),血清TIMP-1含量在ACS组和SA组之间差异无统计学意义(P=0.254),ACS组MMP-9含量与hs-CRP呈正相关(r=0.571,P<0.05),冠状动脉狭窄程度积分与hs-CRP、MMP-9舍量无相关性(r=0.091,P>0.05;r=0.110.P>0.05).结论 hs-CRP、MMP-9的浓度与冠状动脉的狭窄的程度无明显关系,与斑块的稳定性有关,炎症导致了斑块的不稳定性,参与了ACS的发生.     

阿托伐他汀和辛伐他汀对急性冠脉综合征患者MMP-9和IL-6的影响

目的 观察急性冠脉综合征患者早期给予阿托伐他汀和辛伐他汀对血清基质金属蛋白酶-9 (MMP-9)和白介素-6(IL-6)的影响.方法 60例急性冠脉综合征患者随机分为阿托伐他汀20 mg治疗组(阿托伐他汀组)和辛伐他汀40 mg治疗组(辛伐他汀组),分别治疗7 d.测定两组治疗前后血清MMP-9和IL-6的值.同时选30例冠脉造影正常者作为对照组.结果 治疗前阿托伐他汀组和辛伐他汀组血清MMP-9和IL-6的水平均明显高于对照组(P<0.05).阿托伐他汀组和辛伐他汀组治疗后血清MMP-9和IL-6的水平均明显下降,与治疗前比较差异均有统计学意义(P＜0.05).阿托伐他汀组治疗后血清MMP-9和IL-6的水平与辛伐他汀组比较差异有统计学意义(P<0.05).结论 急性冠脉综合征患者初期给予他汀类短期治疗能降低血清MMP-9和IL-6的水平,且阿托伐他汀更明显.     

辛伐他汀对急性冠状动脉综合征患者血清基质金属蛋白酶1、9及其组织抑制因子1的作用

研究认为，基质金属蛋白酶（matrix metalloproternase，MMP）与其组织抑制因子（tissue inhibitom of matris metalloproternase，TIMP）失平衡是造成斑块不稳定的重要原因之一，明胶酶（MMP-1和MMP-9）是MMP家族中的一个重要成员，TIMP-1主要抑制MMP-1及MMP-9的活性，从而阻止纤维帽的降解。本研究观察辛伐他汀对急性冠状动脉综合征（acute coronary syndrome，ACS）患者血清MMP-1、MMP-9和TIMP-1水平的影响，探讨他汀类对稳定斑块的影响。     

阿托伐他汀对急性冠状动脉综合征病人疗效观察

目的研究不同剂量的阿托伐他汀对急性冠状动脉综合征病人血脂、基质金属蛋白酶(matrixmetalloproteinases,MMP)、高敏C反应蛋白C(highsensitivity-Creactiveprotein,hs-CRP)水平和生活质量的影响。方法选取我院急性冠状动脉综合征病人51例,随机分为小剂量治疗组28例,口服阿托伐他汀10mg,每日1次,共30d;大剂量治疗组23例,口服阿托伐他汀80mg,每日1次,共30d,治疗前和治疗30d时测定血脂、MMP-1、MMP-9、金属蛋白酶组织抑制物和hs-CRP,并进行活动平板检查。病人每周接受门诊或电话随访。结果30d后,两治疗组血脂水平、血清MMP-1、MMP-9、hs-CRP水平均降低,两组下降程度差异有统计学意义。胸痛发作次数减少,硝酸甘油用量减少和运动平板运动持续时间增加,两组相比差异有统计学意义(P<0.05)。结论阿托伐他汀治疗可减少急性冠状动脉综合征病人斑块基质成分降解和炎症反应,改善病人生活质量,大剂量阿托伐他汀应用获益更多。     

炎性因子在急性心肌梗死发病中的作用及不同剂量他汀类药物对其影响

目的研究炎性因子在急性心肌梗死发病中的作用及早期应用不同剂量辛伐他汀对急性心肌梗死患者稳定斑块、减少炎症反应的作用。方法将61例急性心肌梗死患者随机分为他汀治疗1组(辛伐他汀20mg/d,n=21)、他汀治疗2组(辛伐他汀80mg/d,n=23)和常规治疗组(不服用任何调脂药物,n=17);于发病48h内和治疗1周后分别测定血清CD40L、基质金属蛋白酶-9(MMP-9)、C-反应蛋白(CRP)水平。另设健康对照组(n=35)与之对照。结果①治疗前急性心肌梗死组的血清CD40L、MMP-9、CRP水平均较健康对照组明显增高(P<0.01)。②急性心肌梗死三组治疗前血浆CD40L、MMP-9和CRP水平差异无统计学意义,常规治疗组治疗后CD40L、MMP-9和CRP水平较治疗前分别降低12%、13%、6%,治疗前后比较差异无统计学意义。他汀治疗1组治疗后CD40L、MMP-9和CRP水平分别降低31%、42%、29%,治疗前、后比较差异有统计学意义(P<0.05)。他汀治疗2组治疗后CD40L、MMP-9和CRP水平分别降低52%、68%、67%,治疗前、后比较差异有统计学意义(P<0.001)。③急性心肌梗死各组在治疗前、后血脂各组分大致相近,差异无统计学意义。结论急性心肌梗死患者存在着动脉粥样硬化斑块不稳定及炎症加速的过程。早期应用大剂量他汀药物,可明显降低血清炎症因子水平,减少患者冠状动脉粥样斑块基质成分的降解和炎症反应,具有稳定斑块作用。     

辛伐他汀对不同血脂水平急性冠状动脉综合征患者血清基质金属蛋白酶水平的影响

目的　研究正常血脂和高血脂急性冠状动脉综合征 (ACS)患者应用辛伐他汀对抑制动脉粥样硬化斑块细胞外基质降解 ,减少炎症反应 ,稳定斑块的作用。方法　采用双盲、随机、对照方法 ,将正常血脂 (NC组 )和高血脂 (HC组 )ACS患者分为他汀治疗组 (辛伐他汀 2 0mg d ,共 8周。NC组 ,n =33;HC组 ,n =36 )和他汀对照组 (NC组 ,n =32 ,HC组 ,n =36 ) ;于治疗前后分别测定血清基质金属蛋白酶 (MMP) 1、MMP 9、基质金属蛋白酶抑制因子 (TIMP) 1、MMP 9 TIMP 1、高敏C 反应蛋白(hs CRP)水平。结果　 (1)治疗前NC、HC各组的血清MMP 1、MMP 9、MMP 9 TIMP 1、TIMP 1、hs CRP水平均较健康对照组 (n =6 0 )明显增高 ,与血脂水平不相关。 (2 )经辛伐他汀治疗 8周后 ,两治疗组血清MMP 1、MMP 9、MMP 9 TIMP 1、hs CRP水平均明显降低 ,血清TIMP 1水平无显著性差异。HC他汀治疗组血清总胆固醇 (TC)、甘油三酯 (TG)、低密度脂蛋白胆固醇 (LDL C)水平明显降低 ,高密度脂蛋白质胆固醇 (HDL C)水平略有上升 ;NC他汀治疗组血清TC、LDL C水平明显下降 ,TG、HDL C水平略有上升和下降 ,但无显著差异。结论　在正常血脂和高血脂ACS患者中 ,早期应用他汀治疗 ,可减少斑块基质成分的降解和炎症反应 ,具有稳定斑块作用。     

基质金属蛋白酶-9及其抑制物在急性冠状动脉综合征中的意义

目的测定急性冠状动脉综合征患者血浆基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9) 和组织金属蛋白酶抑制因子-1(tissue inhibitor metalloproteinase-1,TIMP-1)的变化,探讨MMP-9和TIMP-1 在急性冠状动脉综合征中的作用。方法急性冠状动脉综合征患者30例,稳定型心绞痛患者29例,正常对照17例,用酶联免疫法测定MMP-9和TIMP-1的血浆水平,血脂水平用比浊法测定。结果急性冠状动脉综合征组MMP．9(13±10)μg／L,TIMP-1(1．4±0．2)μg／L,MMP-9／TIMP-1(10±7);稳定型心绞痛组MMP-9 (2．2±0．5)μg／L,TIMP-1(0．7±0．4)μg／L和MMP-9／TIMP-1(3．2±2．0);正常对照组MMP-9(1．7±1．3)μg／L、 TIMP-1(0．6±0．4)μg／L和MMP-9／TIMP-1(5．2±0．9),急性冠状动脉综合征组与稳定型心绞痛组及对照组差异有统计学意义(P<0．01)。三组血脂水平差异无统计学意义。结论 MMP-9、TIMP-1和MMP-9／TIMP-1 在急性冠状动脉综合征患者中显著升高,他们有可能成为ACS患者易损斑块的预测指标。     

急性冠脉综合征患者血清高敏C反应蛋白、基质金属蛋白酶-9与冠状动脉病变程度的相关性研究

目的 探讨急性冠脉综合征患者血清高敏C反应蛋白（hs-CRP）、基质金属蛋白酶-9（MMP-9）与冠状动脉病变程度的关系.方法 将88例急性冠脉综合征患者依据冠状动脉造影结果分为单支病变组（30例）、双支病变组（28例）和多支病变组（30例）,并选择同期冠状动脉造影检查正常者32例为对照组,比较各组hs-CRP、MMP-9的差异,运用Syntax评分评价急性冠脉综合征患者冠状动脉病变程度,通过多元逐步回归分析Syntax评分与各临床资料的相关性.结果 急性冠脉综合征患者血清hs-CRP、MMP-9水平明显高于对照组,并且随着冠状动脉病变严重程度的增加,hs-CRP、MMP-9水平逐渐升高（P＜0.05）.Pearson相关分析显示,hs-CRP与MMP-9呈正相关（r =0.438,P＜0.05）.多元逐步回归分析提示,Syntax评分与hs-CRP、MMP-9水平呈正相关（r分别为0.41和0.57,P＜0.05）.结论 急性冠脉综合征患者血清hs-CRP、MMP-9水平与冠状动脉病变程度相关,冠状动脉病变程度越重血清中hs-CRP、MMP-9的水平越高.     

慢性阻塞性肺疾病患者血清D-二聚体与基质金属蛋白酶-9及其抑制剂的相关性研究

目的 探讨慢性阻塞性肺疾病(COPD)患者急性加重期治疗前后血清D-二聚体、基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶抑制剂-1(TIMP-1)水平的变化并分析其相关性.方法 选择急性加重期COPD患者37例,对照组30例,用酶联免疫吸附试验检测其治疗前后血清中D-二聚体、MMP-9和TIMP-1的水平.结果 (1)COPD组患者治疗前后血清D-二聚体、MMP-9和TIMP-1水平均高于对照组,两组比较差异有统计学意义(P＜0.05),尤其是TIMP-1在两组间差异更为明显(P＜0.01);COPD组治疗后D-二聚体、MMP-9及TIMP-1水平明显低于治疗前(P＜0.05).(2)COPD组治疗前后D-二聚体与MMP-9、D-二聚体与TIMP-1及MMP-9与TIMP-1均呈正相关.结论 COPD急性加重期患者血清D-二聚体、MMP-9及TIMP-1水平增高,体内可能存在高凝状态或血栓前状态,治疗后有一定程度改善;COPD患者血清D-二聚体与MMP-9呈正相关,两者可作为COPD急性加重期的反应因子.     

Enhanced production of MMP-1, MMP-3, MMP-13, and RANTES by interaction of chondrocytes with autologous T cells

It has been reported that T cells and chondrocytes interact through cell surface molecules such as MHC, CD4 or CD8 in osteoarthritis (OA) and T cells are activated. The objective of this study is to investigate the responses of chondrocyte–T cell interaction in terms of metalloprotease (MMP) and chemokine production. Articular cartilage and autologous blood were obtained from patients with OA and fracture who under went prosthetic surgery. Synovial fluid (SF) was collected from OA patients. Isolated chondrocytes were co-cultured with autologous T cells. SF cells were analyzed by immunostaining or Alcian blue staining. The production of MMP-1, MMP-3, MMP-13, and regulated on activation, normal T expressed and secreted (RANTES) was enhanced by direct co-culture compared to indirect co-culture using Transwell. Production ratio of RANTES in OA was significantly higher than non-arthritic samples. CD3 positive mononuclear cells and chondrocyte-like cells were found in SF. Chondrocyte–T cell contact was more adhesive in OA samples. These results showed the production of MMPs and RANTES was enhanced by the interaction and that chondrocyte–T cell contact was possible in vivo.     

Twist1,MMP-2和MMP-9在结直肠癌组织中的表达及意义

目的:研究Twist1、MMP-2和MMP-9蛋白在结直肠癌组织中的表达及其相互关系.方法:建立组织微阵列平台,应用免疫组织化学方法检测92例结直肠癌组织Twist1、MMP-2和MMP-9蛋白的表达情况.结果:结直肠癌中Twist1的表达率为64.1%,MMP-2和MMP-9阳性率分别为66.3%和67.4%;Twi...     

库肯勃瘤组织VEGF,TGF-β1,MMP-2,MMP-9表达的意义

目的:研究VEGF,TGF-β1,MMP-2,MMP-9在卵巢原发上皮性肿瘤、库肯勃瘤中的表达及其相关性,以探讨其在库肯勃瘤发生、发展中的作用.方法:应用免疫组化S-P法检测VEGF,TGF-β1,MMP-2,MMP-9在45例卵巢原发上皮性肿瘤、38例库肯勃瘤中的表达情况.结果:VEGF、TGF-β1在卵巢原发上皮性肿瘤和库肯勃瘤组织中的表达显著高于正常卵巢组织(VEGF:x2=5.318,P=0.021;x2=22.985,P=0.001.TGFβ1:x2=9.778,P=0.002;x2=12.584,P=0.001).MMP-2,MMP-9在正常卵巢组织中表达缺如;VEGF,MMP-2,MMP-9在库肯勃中阳性表达率明显高于卵巢原发上皮性肿瘤(VEGF:x2=13.149,P=0.001;MMP-2:x2=33.668,P=0.001;MMP-9:x2=38.839,P=0.001);TGF-β1阳性表达率在卵巢原发上皮性肿瘤和库肯勃瘤之间无显著差异.VEGF,TGF-β1,MMP-2,MMP-9在卵巢原发上皮性肿瘤、库肯勃瘤中,任意两指标阳性表达均有正相关性(P＜0.05或P＜0.01).结论:VEGF,TGF-β1,MMP-2,MMP-9参与卵巢癌、库肯勃瘤的发生、发展及演进过程,并可为卵巢上皮性肿瘤及库肯勃瘤的鉴别诊断提供一定依据.     

Evaluation of MMP-1, MMP-8, MMP-9 serum levels in patients with adrenal tumors prior to and after surgery

The aim of the study is to evaluate MMP-1, MMP-8 and MMP-9 serum levels in patients with adrenal tumors prior to and after surgery. Metalloproteinase-1 (MMP-1), MMP-8 and MMP-9 serum levels were evaluated in 43 patients operated on at our clinic between 1997-1999. Forty-one (95.3%) patients underwent adrenalectomy. Two (4.7%) patients were disqualified from surgery due to infiltration of adjacent tissues. MMP-1, MMP-8 and MMP-9 serum levels were determined at the admission and in case of surgery again one month after the operation. ELISA assay (K&D) was applied. Tumor type was determined on the basis of clinical, hormonal and histopathological examination. The correlation between MMP levels and tumor sizes was also evaluated. Patients were divided into 6 groups. Group I included 11 patients with adrenocortical carcinoma (4 with Cushing's syndrome and 7 with incidentalomas); group II--6 patients with benign hormonally active adrenocortical adenoma (4 with Cushing's syndrome and 2 with Conn's syndrome); group III--patients with benign, hormonally inactive adenocortical adenoma; group IV--6 patients with benign, hormonally active phaeochromocytoma; group V--4 patients with hormonally inactive phaeochromocytoma; group VI--5 patients with hormonally inactive adrenal tumors of extraglandular origin (2 myolipomas, 2 fibrolipomas, 1 hammartoma). The control group comprised 10 healthy individuals. Increased MMP-8 and MMP-9 levels were noted in patients with benign and malignant adrenal tumors. No increase of MMP levels was found in patients with tumors of extraglandular origin. The increased MMP-8 and MMP-9 levels occurred most frequently in patients with adrenocortical and hormonally active adrenomedullar cancer, and most rarely in patients with hormonally active adrenocortical tumors. MMP-8 and MMP-9 serum levels did not significantly differ between patients with adrenocortical incidentaloma cancers and in patients with benign incidentalomas. MMP-8 and MMP-9 levels were not increased in patients with inoperable adrenocortical cancers. Serum MMP-1 levels were not increased in patients with benign and malignant adrenal tumors. After surgery, MMP-8 and MMP-9 levels decreased significantly in patients with adrenocortical cancers, whereas the decrease of these MMPs in patients with benign tumors, although noticeable, was not statistically significant. MMP-8 and MMP-9 levels decreased significantly in all patients with increased preoperative levels, although they remained higher than the maximum normal values only in few patients (in 7 and 2 patients, respectively). No correlation between the levels of evaluated MMPs and tumor sizes were found.     

肝炎、肝硬化、肝癌及胃癌患者血清MMP—1、TIMP—1以及MMP—1／TIMP—1复合物的检测

目的 检测血清基质金属蛋白酶－1（MMP－1）、组织金属蛋白酶抑制剂－1（TIMP－1）及两者复合物（MMP－1／TIMP－1 com-plex）含量并评价其变化意义。方法 采用双抗体夹心式酶联免疫吸附法（ELISA）对10例健康对照、15例急性肝炎患者、15例慢性活动性肝炎患者;15例晚期肝硬化患者、15例肝癌手术患者、15例晚期肝癌患者以及10例胃癌入院手术患者进行检测。结果 与健康对照组相比,慢性活动对肝炎、晚期肝硬化以及晚期肝癌患者血清TIMP－1水平显著提高;慢性活动性肝炎及肝癌手术患者组血清MMP－1及MMP－1／TIMP－1复合物水平显著下降;急性肝炎及胃癌手术患者血清MMP－1、TIMP－1及MMP－1／TIMP－1复合物含量无显著变化。结论 在慢性活动性肝炎、晚期肝硬化以及肝癌患者存在严重的MMP－1和TIMP－1的失平衡,这种失平衡是这些患者肝脏细胞外基质净沉积的重要原因。MMP－1和TIMP－1在急性肝炎和胃癌患者血清含量总体变化不显著。     

MMP-1、TIMP-1和TNF-α在溃疡性结肠炎中表达的意义

目的研究基质金属蛋白酶-1（MMP-1）及其抑制剂-1（TIMP-1）、肿瘤坏死因子-α（TNF-α）在溃疡性结肠炎（UC）结肠黏膜不同区域以及不同病情中的表达,探讨它们在UC发生发展中的作用和I临床意义。方法收集UC不同区域的结肠黏膜组织,分为轻、中、重三组。采用逆转录-聚合酶链反应（RT—PCR）及免疫组化检测三种因子的表达。结果MMP—1、TIMP—1、TNF-α在溃疡区的表达高于非溃疡区（P〈0．05）。MMP-1、TNF-α及TIMP-1在重型中的表达高于轻型（P〈0．05）。MMP-1／TIMP-1、TNF-α与病情严重程度相关（P〈0．05）。结论结肠黏膜中TNF-α表达升高,引起黏膜组织免疫失调,可能引起MMP-1与TIMP-1表达失衡,在UC的发生发展中起重要作用。MMP-1／TIMP-1和TNF-α可作为评价UC病情的指标。     

Peripheral blood level alterations of TIMP-1, MMP-2 and MMP-9 in patients with type 1 diabetes.

AIM: To determine the plasma levels of enzymes and inhibitors involved in extracellular matrix turnover in patients with Type 1 diabetes with normal renal function. METHODS: Plasma levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were measured in 43 Type 1 diabetic subjects and age- and sex-matched controls. RESULTS: No significant difference in plasma MMP-2 between diabetic patients and controls was observed. MMP-9 was detected in the plasma of 15 diabetic patients (35%), but undetectable in all control subjects (P < 0.015). Plasma TIMP-1 concentrations were significantly elevated (P < 0.001) in diabetic patients compared to controls. There was no correlation observed between MMP-2, MMP-9 and TIMP-1 and similarly between MMP-2, MMP-9 and TIMP-1 and age, duration of diabetes, blood pressure and glycated haemoglobin (HbA1c). CONCLUSIONS: This study has demonstrated alterations in several plasma extracellular matrix modulators in the absence of significant vascular disease.