基质金属蛋白酶/基质金属蛋白酶组织抑制剂与心房颤动

基质金属蛋白酶是一个细胞外基质降解酶家族,基质金属蛋白酶组织抑制剂是其内源性抑制物.二者平衡在细胞外基质合成及降解过程中起重要作用,与心房颤动过程中心房结构重塑,即心房纤维化及心房扩大相关.目前研究显示基质金属蛋白酶/基质金属蛋白酶组织抑制剂失衡与心房颤动的发生、发展及复发相关,抑制基质金属蛋白酶可改善心房重塑并阻止心房颤动进展.恢复基质金属蛋白酶/基质金属蛋白酶组织抑制剂平衡可能成为治疗心房颤动的新型治疗途径.     

基质金属蛋白酶及其组织抑制剂与肿瘤的侵袭和转移

基质金属蛋白酶类（matrix metalloproteinases，MMPs）是降解细胞外基质（extracelluler matrix，ECM）的重要的一组蛋白酶类，其降解ECM的功能在生理上的作用包括伤口愈合、骨吸收、乳腺退化等，在病理生理方面的作用涉及到类风湿性关节炎、冠状动脉疾病及肿瘤等。MMP被认为与肿瘤生长、侵袭、转移有关。许多研究显示肿瘤转移伴有MMPs的过度表达。     

食管癌基质金属蛋白酶及其组织抑制剂表达的研究

浸润和转移是食管癌晚期主要死因之一。近年研究表明 ,基质金属蛋白酶 (ＭＭＰｓ)及其抑制剂 (ＴＩＭＰｓ)在降解细胞外基质过程中起着重要作用[1,2 ] 。为探讨二者与食管癌侵袭转移的关系 ,我们用免疫组化方法对 43例不同分级、分期的食管癌进行了ＭＭＰ 2、ＭＭＰ 3、ＭＭＰ 7、ＭＭＰ 9和ＴＩＭＰ 1、ＴＩＭＰ 2表达的研究。一、材料和方法1.标本来源 :共 43例患者 ,男 32例 ,女 11例 ,年龄 33～ 89岁 ,平均年龄 5 6 .5岁 ,其中Ⅰ期 2例、ⅡＡ期 2 2例、ⅡＢ期 10例、Ⅲ期 9例 ;有淋巴细胞转移者 19例 ;其中鳞状细胞癌 39例 ,基底细胞癌 …     

基质金属蛋白酶组织抑制剂与动脉粥样硬化

基质金属蛋白酶组织抑制剂(TIMPs)在动脉粥样硬化(AS)形成过程中起着十分重要的作用,TIMPs通过抑制基质金属蛋白酶(MMPs)从而可延缓或阻止AS发生和发展.     

基质金属蛋白酶及其组织抑制剂与创面愈合研究进展

基质金属蛋白酶(MMP)是一组锌依赖性肽链内切酶,它们能够降解细胞外基质成分和非基质蛋白。在胚胎形成、正常组织重构、正常伤口愈合等生理过程中以及组织溃疡、肿瘤细胞的转移、类风湿关节炎和肺纤维化等病理过程中MMP均发挥重要作用。本文综述了MMP和金属蛋白酶组织抑制剂(TIMP)的结构、分类、特点和活性调节,并重点阐述了MMP和TIMP在急性和慢性创面中的表达变化及其在糖尿病足难愈或不愈过程中的作用。     

血清基质金属蛋白酶9和组织基质金属蛋白酶抑制剂1与急性脑梗死的临床关系

目的探讨脑梗死患者血清基质金属蛋白酶9(MMP-9)和组织基质金属蛋白酶抑制剂1(TIMP-1)的动态变化及对临床预后的影响。方法选择急性脑梗死患者60例,按照TOAST分型方法将脑梗死患者分为3组,心源性脑栓塞(CE)组,大动脉粥样硬化性卒中(LAA)组,腔隙性脑梗死(SA)组,每组20例;另选健康体检者20例作为对照组,分别测定急性脑梗死患者发病24 h内,第5、10天的血清MMP-9、TIMP-1含量,记录患者入院时的美国国立卫生研究所脑卒中量表(NIHSS)评分;记录发病1、6个月时的Barthal指数(BI)来评价顸后。结果发病后24 h内,脑梗死各组患者血清MMP-9、TIMP-1含量较对照组均明显升高(P<0.05),其中,CE组和LAA组MMP-9、TIMP-1含量持续至第5天仍未下降.而SA组已逐渐降至正常水平。发病后24 h内血清MMP-9含量与相应时间段NIHSS评分呈正相关。近期预后较好患者发病24 h内血清MMP-9含量明显低于预后较差患者(P<0.05)。结论MMP-9与病情的严重程度有关。脑梗死后24 h内的血清MMIP-9含量是预后的独立预测因素。     

基质金属蛋白酶及其抑制剂与心脏重构

本文介绍了基质金属蛋白酶 (MMPs )及其抑制剂新近发现的在心肌重构中的作用 ,选择性表达以及基质金属蛋白酶抑制剂的应用进展。     

基质金属蛋白酶、金属蛋白酶组织抑制剂在心室重构中的作用和调节

心室重构是决定心脏病患者心功能及其预后的主要因素之一 ,是心脏基质成分合成或降解代谢失平衡的结果。心脏基质在维护心脏结构和功能完整性方面起着重要的作用。基质重构引起心肌纤维化和进行性心室扩张 ,最终导致心力衰竭。在心肌中存在的能降解所有心脏基质成分的基质金属蛋白酶 (ＭＭＰｓ) ,是重构过程中心脏基质降解的主要因素。在衰竭的心脏中 ,ＭＭＰｓ活性升高导致纤维胶原降解、细胞外基质重构和进行性心室扩张。ＭＭＰｓ在转录前和转录后水平都可调节 ,而且可通过底物间的相互作用和通过内源性生理抑制剂即金属蛋白酶组织抑制剂 …     

基质金属蛋白酶及其组织抑制剂在胸腔积液诊断中的评价

胸腔积液是最常见的胸膜疾病,病因复杂,诊断困难.近年来,与细胞外基质降解和沉淀有关的基质金属蛋白酶及其组织抑制剂在胸腔积液发生发展过程中的作用得到了更为深入的研究,这也为胸腔积液的诊断和鉴别诊断提供了新的思路.本文对基质金属蛋白酶及其组织抑制剂与各种原因所致胸腔积液的关系作一综述.     

基质金属蛋白酶抑制剂与冠心病

1　基质金属蛋白酶抑制剂 (TissueInhibitorofMet alloproteinases,TIMPs)概述1 .1 　TIMPs的分类与结构TIMPs存在于多种组织中 ,是一种内源性低分子量蛋白质 ,是一种多功能因子家族 ,目前研究发现由 4个成员组成 ,依其被发现的先后顺序分别命名为TIMP1、TIMP2、TIMP3、TIMP4。其中TIMP1、TIMP2、TIMP4为可溶性分泌蛋白 ,TIMP3为不溶性蛋白。TIMP1分子量为 2 90 0 0 ,其转录本长度为 0 .9kb ;TIMP2分子量为 2 1 0 0 0 ,其转录本长度为 1 .0～3.5kb ;TIMP3分子量为 2 1 0 0 0 ,其转录本长度为 1 .2～ 1 .4kb ;TIMP…     

类风湿关节炎血清基质金属蛋白酶-3水平及其影响因素的探讨

目的研究基质金属蛋白酶-3 (matrix metalloproteinase-3,MMP-3)在类风湿关节炎(RA)患者血清中的水平及其相关影响因素,探讨MMP-3在类风湿关节炎发病中的作用机制,比较在RA不同时期,血清MMP-3的变化,为临床治疗、预后判断提供新的理论依据。方法酶联免疫吸附实验(ELISA)测定47例初诊RA患者和31名正常健康对照血清中MMP-3水平。同时测定其治疗前的其他实验室指标:类风湿因子(RF)、抗角蛋白抗体(AKA)、抗核周因子(APF)、血沉(ESR)及手X片。分析各指标之间的关系。结果47例RA患者MMP-3血清水平为(47.3±1.8) ng/ml,对照组为(12.0±1.3) ng/ml,两组比较差异有显著性(P<0.01)。而无论病例组或对照组,其MMP-3水平差异无显著性。MMP-3水平和RA患者的受累关节数目(P<0.05)、X线分期严重程度及ESR (P<0.01)呈正相关;而与年龄、病程长短、晨僵时间、功能分级、RF、AKA、APF、抗CCP抗体水平无明显关系。不同X线分期时,其MMP-3水平确有差别,其中Ⅰ期与Ⅱ期,Ⅰ期与Ⅲ期差异有显著性(P<0.05)。结论MMP-3在RA血清中高水平存在,与性别无关。尽管RA存在显著的个体差异,MMP-3仍可作为除ESR、RF外的反映病情活动的指标。X线Ⅰ期与Ⅱ期时,MMP-3增高最明显。提示血清中出现高水平MMP-3时,应警惕已有关节软骨的破坏,及早积极干     

Inhibitory effect of cyclo-oxygenase-2 inhibitor on the production of matrix metalloproteinases in rheumatoid fibroblast-like synoviocytes

Cyclo-oxygenase (COX)-2 has been associated with inflammation in rheumatoid arthritis (RA), but its role in joint destruction remains unclear. In this study, we investigated the effect on cultured rheumatoid fibroblast-like synoviocytes (FLS) of the selective COX-2 inhibitor celecoxib on the expression of matrix metalloproteinases (MMPs), which play an important role in tissue degradation and angiogenesis in rheumatoid synovium. Treatment with nontoxic doses of celecoxib resulted in dose-dependent inhibition of MMP-1, -2, and -3 secretion from FLS when measured by enzyme-linked immunosorbent assay. Celecoxib suppressed proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) induced augmentation of the gelatinolytic activity on zymography. These results suggest that COX-2 inhibitors might influence matrix degradation or angiogenesis in RA by downregulating the expression of various MMPs in rheumatoid FLS.     

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。     

Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis

We report a 62-year-old man with rheumatoid arthritis (RA) who developed nodulosis after methotrexate (MTX) treatment. The epithelioid cells of nodules were positive for matrix metalloproteinases (MMP)-2, MMP-3, MMP-9, and Ki67. The synovial tissues obtained from the same patient were negative for MMP-3, MMP-9, and Ki67. This study demonstrated that MTX-induced nodules are different from synovial tissues in terms of MMP expression, suggesting the presence of different pathologic mechanisms and differential MTX susceptibility.     

Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis

Abstract

We report a 62-year-old man with rheumatoid arthritis (RA) who developed nodulosis after methotrexate (MTX) treatment. The epithelioid cells of nodules were positive for matrix metalloproteinases (MMP)-2, MMP-3, MMP-9, and Ki67. The synovial tissues obtained from the same patient were negative for MMP-3, MMP-9, and Ki67. This study demonstrated that MTX-induced nodules are different from synovial tissues in terms of MMP expression, suggesting the presence of different pathologic mechanisms and differential MTX susceptibility.     

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.     

Prevalence of rheumatoid arthritis in Antalya, Turkey

The aim of this study was to evaluate the prevalence of rheumatoid arthritis (RA) in Antalya, Turkey. A cross-sectional study was performed face-to-face using a structured interview. Subjects were asked whether they had arthritis at present or previously. Subjects suspected of having RA were invited to the hospital for physical examination and laboratory investigations. Diagnosis of RA was confirmed if the patient fulfilled 1987 American College of Rheumatology (ACR) criteria for RA. A total of 3173 subjects were interviewed. The diagnosis of RA was established in 12 subjects. The prevalence of RA was determined as 0.38% [95% confidence interval (CI): 0.16–0.59]. The mean age was 49.92±11.56 years in subjects with RA and greater than that of other subjects (p<0.001). Of 12 subjects with RA, 9 had previously been diagnosed with the disease. Rheumatoid factor was detected in the sera of eight subjects. RA is less frequent in Turkey than in Northern Europe. Different genetic and environmental factors may have a role in this result.     

Corticosteroid prescribing in rheumatoid arthritis and psoriatic arthritis

Corticosteroid usage was assessed in rheumatoid arthritis (RA) and psoriatic arthritis (PA) patients in Italy. A multicentre, observational study was undertaken in 10 Italian rheumatological centres from 1990 to 1992 using a computerised clinical data bank. Nine hundred and seven RA patients and 180 PA patients were studied; 510 (56.2%) RA patients and 44 (24.4%) PA patients were using corticosteroids. The percentage of patients taking corticosteroids ranged from 20.5 to 85.4% for RA patients and from 0 to 55% for PA patients for the different centres. Methylprednisolone was the most prescribed corticosteroid, both in RA patients (63.2%) and in PA patients (65.9%). The average methylprednisolone daily dose was 5.7±3.6 mg in RA patients and 4.5±1.4 mg in PA patients. The data provide evidence that corticosteroids are taken in an unexpectedly high percentage of patients with RA and PA in Italy.