HMGB1和MMP-9在腹主动脉瘤组织中的表达及临床意义

目的：通过检测高迁移率族蛋白B1（HMGB1）和基质金属蛋白酶-9（MMP-9）在非破裂腹主动脉瘤（AAA）及破裂腹主动脉瘤（RAAA）组织中的定位表达,探讨HMGB1和MMP-9在腹主动脉瘤发病机制中的作用及临床意义。方法：应用免疫组织化学技术,分别检测HMGB1和MMP-9在30例非破裂AAA（包括9例小AAA：横径〈5.0 cm,15例中AAA：横径5.0～7.0 cm,6例大AAA：横径≥7.0 cm）、12例RAAA中的定位表达,并与10例正常腹主动脉组织中HMGB1和MMP-9表达进行对照研究。结果：在非破裂AAA和RAAA组织中HMGB1与MMP-9的表达均明显高于正常腹主动脉（P〈0.05）。在RAAA组织中MMP-9的表达明显高于非破裂AAA（P=0.045）;MMP-9在大AAA和RAAA组织中的表达阳性率明显高于中、小AAA（P=0.010）,而HMGB1在不同大小AAA组织中的表达无差异（P=0.602）。MMP-9在发生心脑血管意外患者中的表达明显高于未发生者（P=0.027）。HMGB1与MMP-9在非破裂AAA组织中的表达无相关性（P=0.767）,在RAAA组织中的表达呈正相关（P=0.016）。结论：MMP-9在AAA扩张甚至破裂中发挥重要作用;HMGB1与MMP-9在RAAA组织中发挥正协同作用;HMGB1和MMP-9在AAA的发病机制中有重要作用。     

基质金属蛋白酶2,9及金属蛋白酶组织抑制剂1在肾盂移行细胞癌中的表达及意义

目的 探讨基质金属蛋白酶2（MMP-2），9（MMP-9）及金属蛋白酶组织抑制剂1（TIMP-1）表达与肾盂移行细胞癌分级、分期及预后的关系。方法 采用免疫组化SP法检测117例肾盂移行细胞癌标本MMP-2，MMP-9发TIMP-1表达水平。患者中男97例，女20例。平均年龄59岁。肿瘤病理分级：G123例、G273例、G321例；TNM病理分期：Ta22例、T127例、T221例、T325例、T422例。结果 肾盂癌组织MMP-2表达阳性率81．2％（95例），MMP-9表达阳性率72．6％（85例），TIMP1表达阳性率72．6％（85例），阳性表达强度和阳性细胞分布不均匀，主要位于肿瘤细胞的胞质，随肿瘤分级、分期增加，MMP-2、MMP-9阳性表达率呈递增趋势，FL与预后相关，差异有统计学意义（P〈0．05）。TIMP-1阳性表达率随分级、分期增加呈递减趋势，但其差异无统计学意义（P〉0．05），TIMP-1表达强度与患者的生存时间无明显相关性。单因素方差分析发现MMP-9／TIMP-1比值与肿瘤临床病理分级、分期密切相关，随着分级、分期增加呈递增趋势（P〈0．05）。结论 MMP-2及MMP-9检测在肾盂癌病理分级、分期中有重要价值。MMP-2、MMP-9及MMP-9／TIMP-1比值在肾盂癌的预后判断中有重要意义。     

MMP-9及TIMP-1在甲状腺癌组织及外周血中的表达及临床意义

目的探讨甲状腺癌组织中基质金属蛋白酶-9（MMP-9）和组织金属蛋白酶抑制剂-1（TIMP-1）的表达,以及血清中MMP-9和TIMP-1浓度与肿瘤浸润、转移的关系。方法采用免疫组织化学SP法测定32例甲状腺癌组织、23例癌旁组织及30例良性甲状腺病变组织标本中MMP-9和TIMP-1的表达,并应用酶联免疫吸附试验（ELISA）方法检测MMP-9和TIMP-1在其中21例甲状腺癌和19例良性甲状腺病变患者外周血清中的浓度。结果MMP-9及TIMP-1在甲状腺癌组织中呈高表达（75.0%、56.3%）,在癌旁组织及良性病变组织中呈低表达（30.4%、21.7%,26.7%、23.3%）,P〈0.05。MMP-9和TIMP-1蛋白的表达与肿瘤浸润程度、淋巴结转移和TNM分期有关（P〈0.05）,MMP-9蛋白表达与TIMP-1蛋白表达呈负相关（r=-0.509,P=0.003）。甲状腺癌组MMP-9和TIMP-1的血清浓度明显高于甲状腺良性疾病组（P=0.000,P=0.037）。甲状腺癌组织中MMP-9和TIMP-1蛋白表达高者相应血清中的MMP-9和TIMP-1浓度也较高（P〈0.05）。结论检测甲状腺肿瘤患者病变组织中MMP-9和TIMP-1的表达情况及外周血中MMP-9和TIMP-1浓度有助于甲状腺良、恶性病变的鉴别诊断,并可作为甲状腺癌预后评估的依据之一。     

MMP-2、MMP-9及其抑制因子TIMP-2、TIMP-1在非黑色素性皮肤癌中的表达及意义

目的：分析MMP-2、MMP-9及其抑制因子TIMP-2、TIMP-1在非黑色素性皮肤癌中的表达情况及临床意义。方法：选取病理证实的SCC患者26例（SCC组）,BCC患者22例（BCC组）。手术切除病变组织,采用SABC法行免疫组化检测,记录各因子表达阳性率、染色强度和表达强度。同时,取20例正常皮肤为对照组。比较SCC组、BCC组患者及对照组各因子表达情况差异。结果：SCC组和BCC组与对照组MMP-2、MMP-9相比,表达阳性率、染色强度和表达强度显著增高,SCC组和BCC组与对照组TIMP-2、TIMP-1的表达阳性率、染色强度和表达强度明显降低（P〈0.05）。SCC组MMP-2、MMP-9的表达强度显著高于和BCC组,而TIMP-1、TIMP-2表达强度显著低于BCC组（P〈0.05）。结论：MMP-2、MMP-9及其抑制因子TIMP-2、TIMP-1与NMSC发生发展密切相关,其可能在NMSC侵袭与转移中发挥重要作用。     

MMP-9、TIMP-1蛋白在门静脉高压脾脏中的表达及临床意义

目的 探讨基质金属蛋白酶-9 （MMP-9）及金属蛋白酶组织抑制因子-1（TIMP-1）在门静脉高压脾脏中表达及临床意义.方法 采用免疫组织化学及免疫印记方法检测门静脉高压脾脏及正常脾脏中MMP-9、TIMP-1的表达情况.分析其与脾脏纤维化程度及与临床资料的关系.结果 门静脉高压脾脏中MMP-9的表达明显低于正常组（P〈0.05）;而TIMP-1蛋白则明显增高（P〈0.05）.（2）MMP-9和TIMP-1表达均与Child-Pugh分级相关.（3）门静脉高压脾脏中MMP-9与脾脏纤维化程度呈显著负相关（r=-0.594,P=0.000）;TIMP-1表达与脾脏纤维化程度呈显著正相关（r=0.630,P=0.000）.结论 MMP-9与TIMP-1在门静脉高压脾脏纤维化过程中具有重要作用.     

MMP-2、TIMP-1、TIMP-2的表达与星形细胞肿瘤生物学行为的演进

目的探讨基质金属蛋白酶2（MMP-2）和基质金属蛋白酶抑制剂（TIMP-1，TIMP-2）在人脑星形细胞的肿瘤中的表达及其与肿瘤临床生物学行为的关系。方法采用免疫组织化学S—P法检测10例正常组织和52例星形细胞肿瘤组织中MMP-2、TIMP-1和TIMP-2的表达情况。结果MMP-2、TIMP-1、TIMP-2在正常脑组织中阳性着色只位于内皮细胞胞浆和基底膜；在星形细胞肿瘤中，还见于部分瘤细胞的胞浆。52例不同病理级别星形细胞肿瘤中MMP2、TIMP-1、TIMP-2阳性表达率（χ^2=6．222～10．185，P〈0．05）和阳性表达强度（H=7．966～10．353，P〈0．05）差异均具有显著性。结论MMP-2、TIMP-1和TIMP-2在星形细胞肿瘤中的表达与星形细胞肿瘤的侵袭性生物学行为的演进密切相关。     

RECK、MMP-2和MMP-9基因在结肠癌组织中的表达及其意义

目的：研究回复引导半胱氨酸丰富蛋白Kazal基元（RECK）、基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）基因在结肠癌中的表达情况及其意义。方法：采用半定量逆转录-聚合酶链反应（RT-PCR）法检测40例结肠癌组织及癌旁组织RECK、MMP-2、MMP-9基因的表达并作相对定量分析。结果：与癌旁组织相比,结肠癌组织中RECK基因表达显著降低（0.46±0.16比0.88±0.08,P〈0.01）,而MMP-2、MMP-9基因表达显著增高（0.41±0.13比0.14±0.13,0.28±0.11比0.12±0.06,P〈0.01）,RECK基因的表达与MMP-2、MMP-9呈显著负相关（r=-0.918,P〈0.01;r=-0.855,P〈0.01）;MMP2、MMP9基因表达水平与淋巴结转移、TNM分期相关;RECK则与肿瘤分化程度、淋巴结转移、远处转移及TNM分期相关。结论：结肠癌组织中存在RECK基因的低表达和MMP-2、MMP-9基因的高表达,其机制可能与RECK抑制MMP-2和MMP-9基因的表达有关。联合检测RECK、MMP2、MMP9基因的表达对结肠癌的诊断以及转移和临床分期的判断具有重要的意义。     

基质金属蛋白酶9、3和金属蛋白酶组织抑制物1在原发性膜性肾病肾小球内的表达及意义

目的探讨基质金属蛋白酶9（MMP-9）、基质金属蛋白酶3（MMP-3）和金属蛋白酶组织抑制物1（TIMP-1）在原发性膜性肾病（IMN）患者肾小球内的表达变化及其与蛋白尿、Scr的关系。方法用免疫组织化学技术分别检测44例IMN患者（IMN组）与6例正常对照者（对照组）肾小球内MMP-9、MMP-3和TIMP-1的表达。结果MMP-9及MMP-3在对照组正常肾组织的肾小管上皮细胞、肾间质和肾小球足细胞有少量表达；在IMN组肾小球足细胞、系膜细胞、肾小球基底膜及肾小管上皮细胞有表达。IMN组肾小球内MMP-9及MMP-3的表达均较对照组显著增强（P〈0．05）。TIMP-1在对照组正常肾组织的肾小管上皮细胞有少量表达，肾小球内无表达；在IMN组肾小球足细胞、肾小管上皮细胞有表达。IMN组肾小球内TIMP-1的表达较对照组显著增强（P〈0．01）。IMN组24h尿蛋白定量显著高于对照组（P〈0．01）。Ⅱ期MN组肾小球MMP-9／TIMP-1及MMP-3／TIMP-1比值较Ⅰ期MN组明显下降（P〈0．01）。IMN组肾小球内MMP-9的表达与Scr呈负相关（r=-0．02，P〈0．05）；TIMP-1的表达与Scr呈正相关（r=0．34，P〈0．05）。结论MMP-9与TIMP-1从正反两方面影响IMN患者肾功能的改变。MMP-9、MMP-3的异常表达与IMN患者蛋白尿之间可能相关；IMN患者肾小球MMP／TIMP比值失衡可能与IMN患者肾小球基底膜增厚相关。     

基质金属蛋白酶-9在腹主动脉瘤体组织中的表达及其临床意义

目的 通过检测基质金属蛋白酶-9（MMP-9）在人腹主动脉瘤（AAAs）组织中的定位表达，探讨MMP-9在腹主动脉瘤发病机制中的作用及临床意义。方法 应用免疫组织化学技术，检测了MMP-9在20例AAAs瘤体组织中的定位表达，并与15例动脉硬化闭塞性疾病（AODs）的病变管壁及10例正常动脉管壁组织中的MMP-9组织学表达进行对照研究。结果 AAAs动脉壁中富含大量MMP-9颗粒，MMP-9阳性表达率达95．0％（19／20）；正常动脉管壁组织未检测到MMP-9的表达；AODs病变血管壁内可见散在分布的MMP-9阳性颗粒，MMP-9阳性表达率为26．7％（4／15）。与AODs和正常动脉管壁相比较，MMP-9在AAAs瘤体组织中的表达差异具有意义（P〈0．01）。结论 腹主动脉瘤体组织中MMP-9的高表达，促进主动脉中层细胞外基质崩解进而导致动脉弹性下降、动脉扩张及进一步的瘤体形成，在AAAs的发病机制中具有重要作用。     

胃癌组织中E-钙黏蛋白、MMP-2蛋白和MMP-9蛋白的表达及意义

目的探索胃癌组织及癌旁组织中E-钙黏蛋白、基质金属蛋白酶-2（MMP-2）及基质金属蛋白酶-9（MMP-9）的表达情况,并分析其表达与胃癌临床病理特征的关系。方法采用ABC免疫组化染色方法检测40例胃癌组织和癌旁组织中E-钙黏蛋白、MMP-2蛋白及MMP-9蛋白的表达情况,比较2种组织中3种蛋白的表达情况;并分析该3种蛋白与胃癌临床病理特征的关系。结果胃癌组织与癌旁组织比较,其E-钙黏蛋白的表达下调（P〈0．05）,而MMP．2蛋白和MMP．9蛋白表达均上调（P〈0．05）。T3＋T4期、N1～N3期及Ⅲ＋Ⅳ期胃癌组织中E-钙黏蛋白的表达阳性率分别低于T1＋T2期、NO期及Ⅰ＋Ⅱ期胃癌组织（P〈0．05）;MI期和Ⅲ＋Ⅳ期胃癌组织中MMP-2蛋白的表达阳性率分别高于M0期和I＋Ⅱ期胃癌组织（P〈0．05）;T3＋T4期、Ⅲ＋Ⅳ期及低-未分化的胃癌组织其MMP．9蛋白的表达阳性率分别高于T1＋T2期、I＋Ⅱ期及高-中分化胃癌组织（P〈O．05）。结论E-钙黏蛋白可能参与胃癌的浸润及淋巴结转移,MMP-2蛋白可能参与胃癌的远处转移,而MMP-9蛋白可能参与胃癌的分化及肿瘤浸润。该3种蛋白可作为判断胃癌分期和预后的指标。     

Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm

BACKGROUND: Loss of elastin is the initiating event in abdominal aortic aneurysm (AAA) formation, whereas loss of collagen is required for continued expansion. The elastolytic matrix metalloproteinases (MMPs) 2 and 9 are well described, but the source of excessive collagenolysis remains undefined. The aim of this study was to determine the expression of MMP-8, a potent type I collagenase, in normal aorta and AAA. METHODS: Infrarenal aortic biopsies were taken from 40 AAA and ten age-matched normal aortas. The concentrations of MMP-8 protein and its inhibitors, tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-2, were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was used to localize MMP-8 expression. RESULTS: MMP-8 concentrations were significantly raised in AAA compared with normal aorta (active MMP-8: 4.5 versus 0.5 ng per mg protein, P < 0.001; total MMP-8: 16.6 versus 2.8 ng per mg protein, P < 0.001). Levels of TIMP-1 and TIMP-2 were significantly lower in AAA than in normal aortic samples (TIMP-1: 142.2 versus 302.8 ng per mg protein; P = 0.010; TIMP-2: 9.2 versus 33.1 ng per mg protein, P < 0.001). Immunohistochemistry localized MMP-8 to mesenchymal cells within the adventitia of the aortic wall. CONCLUSION: The high concentration of MMP-8 in aortic aneurysms represents a potent pathway for collagen degradation, and hence aneurysm formation and expansion.     

基质金属蛋白酶-9及金属蛋白酶组织抑制剂-1对甲状腺乳头状癌诊断的意义

目的:探讨基质金属蛋白酶-9(MMP-9)和金属蛋白酶组织抑制剂-1(TIMP-1)在甲状腺肿瘤组织中的表达。方法:制备组织芯片,采用免疫组织化学和原位杂交技术检测56例甲状腺癌组织、56例癌旁组织和40例良性甲状腺病变组织中MMP-9和TIMP-1的表达情况。结果:MMP-9和TIMP-1蛋白在甲状腺癌组织的阳性表达率为71.4%和57.1%,MMP-9 mRNA和TIMP-1 mRNA在甲状腺癌组织中阳性表达率为67.9%和62.5%,均明显高于癌旁和良性甲状腺病变组织(P<0.05)。在甲状腺癌组织中,MMP-9、TIMP-1蛋白和MMP-9、TIMP-1 mRNA的表达,分别呈负相关性(RS=-0.309、-0.264,P<0.05)。结论:MMP-9和TIMP-1在组织中的检测有助于甲状腺癌的判断,并可作为预后评估的重要参考。     

Matrix metalloproteinases in ascending aortic aneurysms: bicuspid versus trileaflet aortic valves

BACKGROUND: Abnormal matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) expression contributes to the development of abdominal aortic aneurysms. Recent data suggest that MMP-2 and MMP-9 may also play a role in thoracic aortic disease. We sought to determine (1) whether ascending aortic aneurysms are associated with increased MMP expression and (2) whether aortic inflammation and MMP expression differ between patients with congenital bicuspid aortic valves (BAVs) and those with trileaflet aortic valves (TAVs). MATERIALS AND METHODS: Samples of ascending aortic aneurysms were obtained from 29 patients; 14 patients had BAVs and 15 had TAVs. Control ascending aorta was obtained from 14 organ donors or heart transplant recipients. Aortic histology and immunohistochemistry were performed to evaluate elastin degradation, inflammatory changes, and MMP-2 and MMP-9 expression. Aortic levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured using ELISA. RESULTS: Aneurysms in the TAV patients exhibited marked inflammation, high CD68 expression, diminished elastin content, increased MMP-9 expression, and normal MMP-2 levels. In contrast, BAV aneurysms were characterized by a relative lack of inflammation, preservation of elastin content, normal MMP-9 levels, and elevated MMP-2 expression. TIMP-1 and TIMP-2 levels were not significantly different among the three groups. CONCLUSIONS: Ascending aortic aneurysms exhibited increased MMP expression. The pattern of MMP expression and the degree of inflammation, however, differed between aneurysms associated with BAVs and those with TAVs. Variations in the molecular mechanisms underlying different types of thoracic aortic aneurysms warrant further investigation.     

Differential regulation of matrix metalloproteinase activities in abdominal aortic aneurysms

BACKGROUND: The increased synthesis of matrix metalloproteinases (MMPs) by aortic smooth muscle cells (SMCs) is thought to be involved in the etiopathogenesis of abdominal aortic aneurysms (AAAs), but the functional regulation and the activation states of these MMPs remain unclear. In this study, we assessed the expression levels and the functional regulation of several MMPs in the pathogenesis of AAAs. METHODS: Human healthy aorta and AAA specimens were homogenized, and the proteolytic activities of MMP-2 and MMP-9 and of the macrophage metalloelastase (MMP-12) were assessed with zymography. Protein expression of MMP-1, MMP-12, membrane-type 1 MMP (MT1-MMP), tissue inhibitor of MMP 1 (TIMP-1), TIMP-2, TIMP-3, alpha-actin, and beta-actin was analyzed with electrophoresis on sodium dodecyl sulfate gels and immunoblotting. RESULTS: MMP-1, MMP-9, and MMP-12 zymogen levels and proteolytic activities were increased in AAAs when compared with healthy aorta. A severe reduction in alpha-actin--positive vascular SMCs was observed in all the AAA specimens and was correlated with an increase in TIMP-3 but not TIMP-1 or TIMP-2 potential activities. Although pro--MMP-2 activity was decreased, the extent of activated MMP-2 remained unaffected in the AAAs. In accordance with this result, a highly activated MT1-MMP form was also observed in AAAs. CONCLUSION: These data suggest that chronic aortic wall inflammation is mediated by macrophage infiltration, which may account for the destruction of medial elastin, as reflected by SMC down regulation, through increased levels of active MMP-1 and MMP-12. Moreover, altered MT1-MMP proteolytic turnover and differential regulation of TIMP expression in AAAs suggest that tight regulatory mechanisms are involved in the molecular regulation of MMP activation processes in the pathogenesis of AAAs.     

Effects of tissue inhibitor of metalloproteinase 2 deficiency on aneurysm formation

OBJECTIVE: Matrix metalloproteinase (MMP)-2 has been shown to play a pivotal role in aortic aneurysm formation. Its activation requires formation of a trimolecular complex of MMP-2, tissue inhibitor of metalloproteinase-2 (TIMP-2), and membrane type 1 (MT1)-MMP, which is attached to the cell surface. At higher concentrations, TIMP-2 becomes an inhibitor of MMP-2. Thus, TIMP-2 could both augment and inhibit matrix degradation. This study was undertaken to define the net effect of TIMP-2 on matrix destruction and aneurysm formation. METHODS: The abdominal aortas of wild-type and TIMP-2-deficient (TIMP-2 -/-) mice were exposed to 0.25 mol/L CaCl2 or 0.9% NaCl for 15 minutes after laparotomy. Aortic diameters were measured before treatment and 6 weeks after aneurysm induction. In addition, aortic tissues were studied for MMP-2 activation by zymography, and matrix structure was studied by connective tissue staining. RESULTS: The aortic diameter increased in both wild-type and TIMP-2-/- mice. The increase in the TIMP-2 -/- mice was significantly smaller after CaCl2 treatment (51% +/- 3%) compared with the diameter of wild-type mice (67% +/- 4%). Connective staining of aortic sections from the CaCl2-treated mice revealed disruption and fragmentation of the medial elastic lamellae in both wild-type and TIMP-2 -/- mice. Zymographic analysis showed that active MMP-2 levels were decreased in TIMP-2 -/- aortas compared with wild-type mice. CONCLUSIONS: Targeted deletion of TIMP-2 results in attenuation of aneurysm development. Despite its name as an inhibitor of MMPs, TIMP-2 promotes aortic enlargement in vivo, presumably through its role as a cofactor in the activation of MMP-2. CLINICAL RELEVANCE: Abdominal aortic aneurysmal (AAA) disease is a potentially fatal disorder that screening studies have detected in 2% to 9% of the general population. Medical therapy designed to inhibit the progression of small aneurysms includes control of hypertension and smoking cessation; neither of these measures is of proven benefit. Effective and directed medical treatments for small AAAs await elucidation of key etiologic factors. Understanding precisely which molecules mediate AAA development, and blocking the activity of these molecules, could lead to important new therapies. Through our research, we have found that tissue inhibitor of metalloproteinase (TIMP)-2 has a role in this process in an experimental model of aortic aneurysms. We believe that TIMP-2 promotes aortic enlargement in vivo by activating matrix metalloproteinase 2.     

Matrix metalloproteinase expression in the ascending aorta and aortic valve

Extracellular matrix degradation and increased proteolytic enzyme (matrix metalloproteinase (MMP)) activity characterise abdominal aortic aneurysm formation. Post-stenotic dilatation of ascending aorta is associated with aortic stenosis and regurgitation, haemodynamically normal bicuspid aortic valve (BAV) and following AV replacement. We aimed to determine an association between ascending aortic pathology and abnormal AV, with particular reference to MMPs, and ascertain differences between BAV and tricuspid (TAV) AV. Subset of the study population (n=19) with a preoperative ascending aorta of >4 cm was analysed. Samples of ascending aorta and AV were obtained from 82 patients (TAV, n=54, BAV, n=28) undergoing surgery. Gene expression of MMP-1, -2, -9 and tissue inhibitor of metalloproteinase (TIMP)-1 and -2 was quantified by real-time RT-PCR. No significant difference was seen in gene expression level of MMPs, TIMPs and ratio of MMPs/TIMPs in ascending aorta and AV between patients with BAV and TAV. MMP-2/TIMP-1 in ascending aorta was greater in BAV, in the subset of patients with preoperative aortic dilatation (P<0.05). No difference exists in gene expression of MMPs in ascending aorta and AV between patients with BAV and TAV. However, patients with larger aortic diameters have increased MMP-2/TIMP-1. Modifying MMP expression may have a role in development of aneurysms.     

Matrix metalloproteinase expressions in arteriosclerotic aneurysmal disease

Medial degeneration of extracellular matrix (ECM) proteins in the wall of abdominal aortas results in smooth muscle cell destruction, a loss of architectural integrity, and abdominal aortic aneurysm (AAA) formation. It has been theorized that an imbalance between proteinases and their naturally occurring inhibitors is the cause of these observed histologic abnormalities. Therefore, the purpose of this investigation was to determine if differences in the matrix metalloproteinase (MMP) -2 and -9, tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) protein and activity levels existed between infrarenal AAA and normal abdominal aortic tissue specimens. Between November 1995 and January 1997, 10 patients undergoing elective infrarenal AAA repair had a portion of their aneurysm walls snap frozen in liquid nitrogen and processed for subsequent western blot or zymographic analysis. Tissue specimens from 6 normal abdominal aortas obtained from fresh cadaver specimens were similarly processed and served as controls. Protein levels for MMP-2, MMP-9, TIMP-1, uPA, and tPA were analyzed by western blotting. The degree of MMP-2 and MMP-9 gelatinolytic activity was analyzed by zymography. Detection and immunolocalization for MMP-2, MMP-9 and CD68 was performed on tissue sections of AAA and normal infrarenal abdominal aortas fixed in 10% formalin. MMP-9 and tPA protein levels were increased in AAAs compared to controls by western blotting. However, uPA levels were slightly increased in controls. No differences in TIMP-1 protein levels were identified. Similarly, zymography demonstrated increased MMP-2 and MMP-9 gelatinolytic activity in AAAs compared to controls (p < or = 0.05). CD68-positive cells (macrophages) in the adventitia and media demonstrated immunoreactivity to MMP-9. This investigation demonstrated increased MMP-9 proteinase activity and tPA protein levels in the walls of AAAs, as well as inflammatory leukocyte invasion of the adventitia and media compared to controls. These data suggest that leukocyte-derived MMP-9 is associated with aortic wall degeneration and aneurysm formation. Furthermore, activation of MMP-9 may be caused by increased tPA levels in the walls of AAAs.     

基质金属蛋白酶在腹主动脉瘤组织中的表达

目的探查基质金属蛋白酶类（MMPs）在腹主动脉瘤（AAA）组织中产生的源泉。方法采用间质胶原酶（MMP-1）和明胶酶以MMP-9）的mRNA探针在20例AAA组织及4例正常人腹主动脉组织的切片上行原位杂交实验结果MMP-1及MMP-9在巨噬细胞、平滑肌细胞和淋巴细胞均有表达,其中巨噬细胞的MMPs表达强烈。结论MMPs在AAA的形成和扩张中发挥重要作用,炎性细胞是产生MMPS的主要源泉,并影响问质细胞的MMPS表达。     

u-PA和明胶酶A、B蛋白在人腹主动脉瘤组织中表达的研究

目的 探讨尿激酶型纤溶酶原活化物(u-PA)和明胶酶A、B在腹主动脉瘤(AAA)组织中蛋白的表达和产生的来源。方法 用u-PA和明胶酶A(MMP-2)、明胶酶B(MMP-9)的单克隆抗体,以免疫组织化学SABC方法在10例AAA组织和10例正常腹主动脉组织的切片上控测u-PA和MMP-2、MMP-9抗原(蛋白)。结果 u-PA和MMP-9蛋白在AAA组织中主要浸润于中层和外膜巨噬细胞表达,在正常腹主动脉组织中无表达,MMP-2蛋白在AAA组织中主要由中层平滑肌细胞表达,在正常腹主动脉组织中无表达。结论 由巨噬细胞产生的u-PA直接激活,并调节MMP-2和MMP-9的活性,在AAA的形成、扩张和破裂中起着关键性的作用。