基质金属蛋白酶及其抑制剂在乳腺癌转移、浸润中的作用

目的 :探讨基质金属蛋白酶 (MMP 2、MMP 9)及其抑制剂 (TIMP 1、TIMP 2 )与乳腺癌的关系。方法 :应用免疫组化S P法检测乳腺癌中MMP 2、MMP 9、TIMP 1、TIMP 2的表达。结果　 30例乳腺癌患者中MMP 2阳性表达 14例 ,占 46 7% ,MMP 9阳性表达 16例占 5 3 3% ,TIMP 1阳性表达 4例 ,占 13 3% ,TIMP 2阳性表达 3例 ,占 10 0 %。MMP 2、MMP 9的表达与乳腺癌的淋巴结状况、肿瘤大小相关 ,与年龄、月经状况无关。结论 :MMP 2、MMP 9的表达可以作为估计乳腺癌预后及术后综合治疗的生物学指标     

腹主动脉瘤的发病机制

腹主动脉瘤的形成是解剖学、遗传学、环境学和生物化学诸因素相互影响和共同作用的结果。中膜细胞外基质代谢失衡在腹主动脉瘤的形成中起主要作用。其中基质金属蛋白酶活性增加和弹力蛋白与胶原的基因表达失衡可能是其原因。腹主动脉壁的自身免疫反应性炎症和平滑肌细胞凋亡可影响基质金属蛋白酶和弹力蛋白与胶原合成。     

基质金属蛋白酶及其抑制剂在器官纤维化中的研究进展

器官纤维化共同的基本特征是ECM过度沉积和组织结构改建 ,而病变组织内ECM降解减少是导致其过度沉积的主要原因之一。正常或异常的ECM代谢基于基质降解限速酶MMPs及其抑制剂TIMPs的平衡或失衡 ,MMPs/TIMPs受多种细胞因子和转录因子的调节 ,对肺、肝、肾等器官纤维化的发生、发展及其临床监测与治疗具有重要意义。     

基质金属蛋白酶及其抑制剂在子宫内膜异位症中的研究进展

经血逆流是腹腔子宫内膜异位症的主要发病机制之一,子宫内膜植入其他组织的过程需要细胞外基质的降解,基质金属蛋白酶是降解细胞外基质的重要酶类。近年来研究表明,基质金属蛋白酶及其抑制剂的异常表达在子宫内膜异位症的发生和发展过程中起着重要作用。     

基质金属蛋白酶及其抑制剂与疾病的关系

基质金属蛋白酶（ＭＭＰ）和金属蛋白酶组织抑制剂（ＴＩＭＰ）是细胞外基质（ＥＣＭ）合成及降解代谢平衡调节中两个重要的酶系。ＭＭＰ分为三类，可水解各类胶原及基质糖蛋白、蛋白多糖等成分。ＴＩＭＰ也有三种，均能与ＭＭＰ成员结合成复合物而抑制其活性。两大酶系的调节异常可导致ＥＣＭ的代谢失衡，在器官硬化、肾脏疾病及肿瘤浸润等多种病理过程中起到十分重要的作用。     

基质金属蛋白酶及其抑制剂在家兔血管成形术后血管重构中的作用

目的：探讨基质金属蛋白酶及其抑制剂（MMPs/TIMPs）在家兔血管成形术后血管重构中的作用及中药通心络的影响。 方法： （1）家兔65只分4组（对照组5只，拉伤组20只，高脂组20只，通心络组20只）采用高胆固醇（1.5 g·kg-1·d-1）喂养加两次腹主动脉损伤的方法制成动脉粥样硬化和血管成形术模型， X光下行血管成形术。术后分别治疗4周处死，取血管标本进行检测。（2）HE染色计算机图像分析血管形态的变化。（3）MMP2和TIMP1免疫组化分析，RT-PCR方法测定MMP2、TIMP1的mRNA表达量。 结果： （1）HE染色证实有动脉粥样硬化斑块形成，腹主动脉造影显示有管腔狭窄。（2）RT-PCR结果显示通心络组的MMP2和TIMP1 mRNA表达量低于高脂拉伤组P<0.05； MMP2和TIMP1比值更接近1。（3）免疫组化染色通心络组MMP2和TIMP1的阳性细胞吸光度(%)明显低于高脂拉伤组，P<0.05。（4）内膜面积通心络组低于高脂拉伤组P<0.05；而管腔面积高于高脂拉伤组P<0.05；并且管腔面积的增加与内膜面积的减少不相等。 结论： MMP2和TIMP1参与家兔血管成形术后的血管重构，通心络可以调整MMP2和TIMP1的比值。     

基质金属蛋白酶及其抑制剂在子宫内膜异位症中的研究进展

经血逆流是腹腔子宫内膜异位症的主要发病机制之一，子宫内膜植入其他组织的过程需要细胞外基质的降解，基质金属蛋白酶是降解细胞外基质的重要酶类。近年来研究表明，基质金属蛋白酶及其抑制剂的异常表达在子宫内膜异位症的发生和发展过程中起着重要作用。     

基质金属蛋白酶在心肌缺血大鼠心室间质重构中的作用

目的:探讨大鼠心肌缺血后心肌间质基质金属蛋白酶(MMPs)活性变化与心室间质重构的关系。方法:用异丙肾上腺素(ISP)复制大鼠心肌缺血模型,用酶谱法测定心肌间质MMPs活性,氯胺T法测定胶原含量,免疫组化法测定I/III胶原比例,电镜观察心肌超微结构。结果:心肌缺血组(M组)MMP-2活性在1、2、4周分别是对照组(C组)的5.8倍、2.3倍(P＜0.01)和1.7倍(P＜0.05),MMP-9活性则分别是对照组的4.9倍、1.9倍(P＜0.01)和1.4倍(P＜0.05)。胶原含量、I/III胶原比例在2周、4周时均显著高于对照组。电镜见缺血组心肌细胞坏死、间质胶原大量增生、结构紊乱。结论:心肌缺血后心肌间质内MMPs活性升高,可能是心室重构的重要原因。     

基质金属蛋白酶在多发性硬化发病中的作用机制及治疗现状

多发性硬化（MS）是中枢神经系统炎性脱髓鞘疾病,基质金属蛋白酶是一组蛋白水解酶,有重要的病理和生理作用,近年的研究表明它在（MS）的发生和疾病进展中都具有重要作用,参与主要的发病过程,具有多种发病机制,抑制其活性具有有效的治疗意义。     

基质金属蛋白酶抑制剂与肿瘤关系研究进展

基质金属蛋白酶抑制剂是一组特异性抑制基质金属蛋白酶活性的多功能细胞因子家族,在多种肿瘤中均存在高表达,且与肿瘤的侵袭和转移密切相关,在肿瘤治疗方面是一大研究热点。本文就近年来基质金属蛋白酶抑制剂与肿瘤的相关性研究进展进行综述。     

Inflammatory abdominal aortic aneurysms: A disease entity?

Summary Sixty inflammatory aortic aneurysms of unknown aetiology were examined by serial sections. The histological findings failed to reveal significant differences in either thoracic or abdominal aneurysms with or without marked adventitial fibrosis. Their identical morphology does not favour the existence of a special disease entity of so-called inflammatory abdominal aortic aneurysms (IAAA). Absence or existence of giant cells of any type, occurrence of plasma cells, eosinophils, granulomas, fibrinoid necrosis and adventitial fibrotic thickening cannot be considered as variables which help in differentiation. IAAA are characterized by a marked predominance of male patients and a rather benign clinical course. They usually affect the age group around 60 years. They are not rare and do not seem to be restricted to certain races. Their aetiology, like that of the cases affecting the thoracic aorta (Takayasu's disease, non-specific aortitis) remains unknown, although autoimmune diseases, the retroperitoneal fibrosis of Ormond and arteriosclerosis may be related. However, on the basis of the present evidence we cannot consider them to be one of these diseases. There are no morphological findings which would justify the separation of IAAA from Takaysu's disease.     

Functional characterization of T cells in abdominal aortic aneurysms

Abdominal aortic aneurysms (AAA) exhibit features of a chronic inflammatory disorder. The functional attributes of the T cells in AAA tissue are unclear, with little quantitative or functional data. Using a novel, non-enzymatic method to isolate viable cells from AAA tissue, functional properties of AAA T cells were investigated for the first time. Composition and phenotype of AAA T cells was determined by flow cytometry and verified by immunohistochemistry. Tissue mononuclear cells (MNCs) were cultured in the presence of T-cell mitogens, and cell cycle analysis and cytokine production assessed. Typical cell yield was 4.5 x 10(6) cells per gram of AAA tissue. The majority (58.1+/-5.3%) of haematopoietic (CD45+) cells recovered were CD3+ T cells, B cells comprised 41.1+/-5.7%, natural killer cells 7.3+/-2.5%, and macrophages 2%. Freshly isolated T cells were in resting (G1) state, with 25% expressing the activation-associated cell surface antigens major histocompatibility complex II and CD25. When stimulated in vitro, a significant proportion entered S and G2 phase of the cell cycle, up-regulated CD25, and secreted tumour necrosis factor-alpha, interferon-gamma, interleukin (IL)-5 and IL-6. Despite patient differences, the composition of the AAA inflammatory infiltrate was remarkably consistent, and when re-stimulated ex-vivo T cells produced a stereotypical cytokine response, consistent with the hypothesis that AAA T cells can promote tissue inflammation by secretion of proinflammatory cytokines, and in addition provide signals for B-cell help.     

膝关节软骨中基质金属蛋白酶13及其组织抑制剂1的表达

背景：基质金属蛋白酶组织抑制剂1是与基质金属蛋白酶13相对应的拮抗剂,两者间表达水平和功能活性的平衡对细胞外基质的代谢状态起着重要作用,但在DH豚鼠骨关节炎发生发展过程中,两者表达水平,尤其两者表达水平比值的变化尚不明确。 目的：探讨不同月龄DH豚鼠关节软骨中基质金属蛋白酶13、基质金属蛋白酶组织抑制剂1表达比值的变化及其与DH豚鼠增龄性原发骨性关节炎发病过程中软骨退变程度的关系。 方法：选取2,4,8,12月龄雌性DH各6只,取膝关节观察关节软骨的大体形态后常规脱钙、包埋、制作石蜡切片,用于VG染色行组织学观察,采用Mankin评分系统定量分析关节软骨退变情况,采用免疫组织化学方法检测膝关节软骨中基质金属蛋白酶13、基质金属蛋白酶组织抑制剂1表达情况,应用 Image pro-Plus 6.0软件对免疫组织化学阳性蛋白表达情况进行积分吸光度计算。线性回归分析判断Mankin评分与基质金属蛋白酶13/基质金属蛋白酶组织抑制剂1比值的相关性。 结果与结论：DH豚鼠2月龄膝关节软骨无关节炎表现,4 月龄出现轻度软骨退变,并随月龄增加进行性加重,Mankin评分随月龄增加逐渐增高,各组之间的差异均有显著性意义(P < 0.05)。基质金属蛋白酶13、基质金属蛋白酶组织抑制剂1的表达均随月龄进行性增加,两者比值与Mankin评分呈正相关性(P < 0.05)。结果提示DH豚鼠4月龄出现膝关节软骨退行性变化,随月龄增加而进行性加重,其病理改变与基质金属蛋白酶13/基质金属蛋白酶组织抑制剂1表达失衡有关。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

异种移植建立的大鼠腹主动脉瘤形态学特征

目的: 建立和鉴定一种新型腹主动脉瘤动物模型, 为腹主动脉瘤的进一步研究提供基础。方法: 选取豚鼠肾下腹主动脉组织1 cm, 正位替换SD大鼠同长度腹主动脉; SD大鼠腹主动脉原位离断后吻合分别作为对照。分别于术后4周动态观测和比较移植腹主动脉直径、腔面积等形态学变化; 计算机图像技术半定量分析弹力纤维、胶原纤维及平滑肌变化。结果: 存活受体中88%移植腹部主动脉血流通畅, 无移植物或吻合口狭窄, 无腔内血栓形成。4周内, 异种移植组腹主动脉直径随时间延长逐渐扩张, 与对照组有显著差异; 腹主动脉扩张率与弹力蛋白、中膜平滑肌变化呈现显著负相关。结论: 免疫炎症损伤介导的豚鼠-SD大鼠异种移植腹主动脉瘤是一稳定可靠的动物模型。     

BAK1 gene variation and abdominal aortic aneurysms

We sought to examine the role of genetics in the multifactorial disease, abdominal aortic aneurysm (AAA), by studying sequence variation in the BAK1 gene (BAK1) that codes for an apoptotic‐promoting protein, as chronic apoptosis activation has been linked to AAA development and progression. BAK1 abdominal aorta cDNA from AAA patients and nondiseased individuals were compared with each other, as well as to the BAK1 genomic sequence obtained from matching blood samples. We found specific BAK1 single nucleotide polymorphism (SNP) containing alleles in both aneurysmic (31 cases) and healthy aortic tissue (5 cases) without seeing them in the matching blood samples. These same BAK1 SNPs have been reported, although rarely (average frequency <0.06%), in reference BAK1 DNA sequences. Based on this and other similar observations, we propose a novel hypothesis postulating that multiple variants of genes may preexist in “minority” forms within specific nondiseased tissues and be selected for, when intra‐ and/or extracellular conditions change. Therefore, the fact that different BAK1 variants can exist in both diseased and nondiseased AA tissues compared to matching blood samples, together with the rare occurrence of these same SNPs in reference sequences, suggests that selection may be a significant factor in AAA ontogeny. Hum Mutat 30:1–5, 2009. © 2009 Wiley‐Liss, Inc.     

MiR-30c-1-3p targets matrix metalloproteinase 9 involved in the rupture of abdominal aortic aneurysms

Journal of Molecular Medicine - Abdominal aortic aneurysm (AAA) can be fatal if ruptured, but there is no predictive biomarker. Our aim was to evaluate the prognostic potential of microRNAs...     

Genetic and epigenetic regulation of abdominal aortic aneurysms

Abdominal aortic aneurysms (AAAs) are focal dilations of the aorta that develop from degenerative changes in the media and adventitia of the vessel. Ruptured AAAs have a mortality of up to 85%, thus it is important to identify patients with AAA at increased risk for rupture who would benefit from increased surveillance and/or surgical repair. Although the exact genetic and epigenetic mechanisms regulating AAA formation are not completely understood, Mendelian cases of AAA, which result from pathologic variants in a single gene, have helped provide a basic understanding of AAA pathophysiology. More recently, genome wide associated studies (GWAS) have identified additional variants, termed single nucleotide polymorphisms, in humans that may be associated with AAAs. While some variants may be associated with AAAs and play causal roles in aneurysm pathogenesis, it should be emphasized that the majority of SNPs do not actually cause disease. In addition to GWAS, other studies have uncovered epigenetic causes of disease that regulate expression of genes known to be important in AAA pathogenesis. This review describes many of these genetic and epigenetic contributors of AAAs, which altogether provide a deeper insight into AAA pathogenesis.     

人腹主动脉瘤平滑肌细胞表型变化

目的:研究腹主动脉瘤(AAA)中血管平滑肌细胞(VSMC)表型改变,探讨其在AAA发病中的作用。方法:选取人体AAA、动脉闭塞性疾病(AOD)和正常腹主动脉(NA)组织,采用α-肌动蛋白(α-SMA)、结蛋白(desmin)及肌球蛋白重链3种表型(SM1、SM2和SMemb)单克隆抗体,利用免疫组化及电镜技术,检测VSMC收缩型与合成型。结果:AOD及NA中VSMC以收缩表型α-SMA、desmin、SM1和SM2表达为主,SMemb在AOD的表达较低,而在NA无表达。AAA中VSMC以合成表型SMemb为主,α-SMA、SM1和SM2明显低于AOD及NA,desmin不表达;其中破裂者的SMemb和SM2低于非破裂者。结论:VSMC表型变化参与腹主动脉壁损伤重构,促进AAA形成和发展。     

Topology of the fibrinolytic system within the mural thrombus of human abdominal aortic aneurysms

Development and progression of acquired abdominal aortic aneurysms (AAAs) involve proteolytic activity. In the present study, we investigate the distribution of fibrinolytic system components within mural thrombi of human AAAs. 20 mural thrombi and the remaining AAA walls were dissected. The luminal, intermediate and abluminal thrombus layers, and media and adventitia were separately incubated in cell culture medium. Conditioned media were then analysed for plasminogen activators (PAs), plasminogen activator inhibitor-1 (PAI-1), free-plasmin, plasmin alpha(2)-antiplasmin complexes (PAPs) and D-dimers release. In parallel, PA and PAI-1 mRNA expression analysis was performed by RT-PCR. The study was completed by immunohistochemical localization of these components in AAA, ex vivo functional imaging using (99m)Tc-aprotinin as a ligand and measurement of PAP and D-dimer plasma levels. All fibrinolytic system components were present in each aneurysmal layer. However, the mural thrombus was the main source of active serine-protease release. Interestingly, the luminal layer of the thrombus released greater amounts of PAPs and D-dimers. This paralleled the preferential immunolocalization of plasminogen and PAs, and the (99m)Tc-aprotinin scintigraphic signal observed in the luminal pole of the thrombus. In contrast, mRNA expression analysis showed an exclusive synthesis of tPA and PAI-1 within the wall, whereas uPA mRNA was also expressed within the thrombus. Taken together, these results suggest that the increased plasma concentrations of PAPs and D-dimers found in AAA patients are related to mural thrombus proteolytic activity, thus explaining their known link with AAA progression. Components of the fibrinolytic system could also represent a target for functional imaging of thrombus activities in AAA.     

Open and endovascular repair of juxtarenal abdominal aortic aneurysms: a systematic review

This systematic review focuses on the 30-day mortality associated with open surgery and fenestrated endografts for short-necked (<15 mm) juxtarenal abdominal aortic aneurysms. A search for studies published in English and indexed in the PubMed and Medline electronic databases from 2002 to 2012 was performed, using “juxtarenal abdominal aortic aneurysm” and “treatment” as the main keywords. Among the 110 potentially relevant studies that were initially identified, eight were in accordance with the inclusion criteria in the analysis. Similar outcomes for open and endovascular repair were observed for 30-day mortality. No differences were observed regarding the secondary outcomes (duration of surgery, hospital stay, postoperative renal dysfunction and late mortality), except that the late mortality rate was significantly higher for the patients treated with open repair after a median follow-up of 24 months. Fenestrated endografting is a viable alternative to conventional surgery in juxtarenal abdominal aortic aneurysms with a proximal neck <15 mm.