扩张型心肌病大鼠肿瘤坏死因子α及基质金属蛋白酶1的表达

目的探讨扩张型心肌病对大鼠左心室肌肿瘤坏死因子α(TNF-α)和基质金属蛋白酶1(MMP1)表达水平的影响及与二者的关系。方法用呋喃唑酮饲养大鼠4～8周,超声心动图检测大鼠左心室结构和功能,HE和VG染色分别观察大鼠心肌细胞和问质胶原纤维的变化,RT-PCR检测左室心肌MMP1 mRNA的表达水平,免疫组化检测左室心肌组织TNF-α和MMP1表达水平。结果扩张型心肌病的大鼠左心室增大,收缩功能下降;心肌细胞肥大、变性,问质纤维明显增生;左室心肌组织TNF-α和MMP1表达水平上调。结论扩张型心肌病的大鼠左室肌TNF-α和MMP1的表达水平上调,两者在心肌纤维化及左室重构中起重要作用;TNF-α等细胞因子的激活伴有MMP1表达上调。     

肺癌金属蛋白酶、金属蛋白酶抑制因子表达和细胞凋亡与预后的相关性

目的：研究人肺癌组织中金属蛋白酶,金属蛋白酶抑制因子的表达和细胞调亡与病人预后的关系。方法：应用免疫组化法测MMPs、TIMPs在肺癌标本中的表达、用原位杂交法(ISH)测TIMP1mRNA、用TUNEL法测细胞凋亡。结果：MMP2与MT1-MMP表达十分相近;TIMP1-2在Ⅲ、Ⅳ期肿瘤中强阳性表达明显高于Ⅰ、Ⅱ期肿瘤;NSCLC术后存活4年以下者其MMP1、MT1-MMP、MMP2蛋白强阳性表达率和显著高于4年以上存活者细胞凋亡指数。结论：MMP1-2、TIMP1-2在肺癌组织中的表达强度与肿瘤的分期相关,MMP2与MT1-MMP的表达密切相关且与病人预后有相关性,TIMP3的表达和细胞凋亡与病人预后有相关性。     

基质金属蛋白酶-9、金属蛋白酶抑制因子-1及CD147在食管鳞状细胞癌组织中的表达

目的探讨基质金属蛋白酶-9（MMP-9）、金属蛋白酶抑制因子-1（TIMP-1）及CD147在食管鳞状细胞癌（鳞癌）的表达及意义。方法选择2005年1月～2007年1月在新乡医学院第一附属医院胸心外科行食管癌根治术切除的标本52例，术后均经病理证实为食管鳞癌。采用免疫组织化学方法检测食管癌组织及癌旁正常食管组织中MMP-9、TIMP-1及CD147的表达。结果食管鳞癌组织中MMP-9、TIMP-1及CD147的阳性表达率分别为73．0％、44．2％和80．8％，与癌旁正常食管组织（23．1％、30．8％、19．2％）比较有显著性差异（P〈0．05）。鳞癌组织中MMP-9阳性表达率与TIMP-1无明显相关性（P〉0．05），与CD147成正相关（r=0．457，P〈0．05）。MMP-9阳性表达率与肿瘤浸润及淋巴结转移有关（P〈0．05）。结论食管鳞癌组织中MMP-9／TIMP—1失衡参与了其侵袭转移过程，CD147可能作为涛导剂促进了MMP-9的表达。     

三类TACE抑制剂的作用机理探讨

目的 :以脂多糖 (LPS)刺激的HL 6 0细胞系为天然模型 ,筛选肿瘤坏死因子α转换酶的抑制剂 ,为人工干预炎症过程提供依据和手段。方法 :分时相刺激HL 6 0细胞后 ,用分子生物学和细胞学技术在蛋白质和mRNA水平上研究TACE表达和活性的改变。结果 :中药热毒清 (RDQ)能明显降低LPS诱导的TACEmRNA增加 (与对照组比 ,P <0 .0 1) ;针对TACEmRNA的反义寡核苷酸 (anti ODN)在翻译水平上抑制TACE表达 ,抑制率达 78.9% ;化学合成的针对TACE催化域的小分子底物模拟肽可抑制LPS诱导的TACE表达增加 ,从而抑制sTNFα分泌增加 ,削弱LPS诱发的炎性病理反应强度。结论 :3种不同类型的抑制 (RDQ、anti ODN、底物模拟肽 )在不同层次上调节TACE的表达 ,最终均抑制了sTNFα的分泌 ,为控制炎症提供了明确的治疗靶标。     

PPARs配体对巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子表达的影响

目的：观察PPAR α、γ配体对巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子(EMMPRIN)表达的影响。方法：体外诱导THP-1单核细胞转化为巨噬细胞、泡沫细胞，分别加入PPAR α配体氯贝特（clofibrate）、PPARγ配体吡格列酮(pioglitazone)共同培养，应用Real-time RT-PCR和Western blotting测定巨噬细胞、泡沫细胞中EMMPRIN基因和蛋白表达，ELISA测定细胞培养上清液MMP-9浓度，Zymgraphy法测定MMP-9活性。结果：氯贝特和吡格列酮均能显著抑制巨噬细胞和泡沫细胞EMMPRIN的表达，此抑制作用与PPAR α、γ配体抑制MMP-9分泌及活性的趋势一致。结论：PPAR α、γ配体均可抑制巨噬细胞、泡沫细胞EMMPRIN的表达，下调EMMPRIN可能是PPARs配体抑制粥样斑块局部MMPs产生的机制之一。     

基质金属蛋白酶-9及金属蛋白酶组织抑制因子-1在妊娠期高血压疾病患者胎盘组织中的表达

目的通过研究基质金属蛋白酶-9（MMP-9）及金属蛋白酶组织抑制因子-1（TIMP-1）在正常妊娠和妊娠期高血压疾病患者胎盘中的表达,探讨其与妊娠期高血压疾病发病机制的关系。方法收集山西医科大学第一医院产科和山西中医学院中西医结合医院产科住院分娩的产妇胎盘标本共142例,正常妊娠胎盘组织标本40例为对照组,妊娠期高血压疾病患者胎盘组织标本102例为病例组,通过免疫组织化学二步法,对MMP-9和TIMP-1在胎盘组织中的表达进行检测。结果1.MMP-9及TIMP-1在胎盘组织中的表达部位。在正常妊娠胎盘组织的滋养细胞、蜕膜细胞、间质细胞和血管内皮细胞胞浆中均可见MMP-9、TIMP-1的阳性表达,多为中度阳性和强阳性表达,但在妊娠期高血压疾病患者胎盘组织中,MMP-9未见间质细胞和血管内皮细胞有阳性表达,且表达者多为弱阳性。2.MMP-9在妊娠期高血压疾病患者中的阳性表达与正常妊娠组相比,差异有显著性（P〈0.05）,妊娠期高血压、子痫前期轻度、子痫前期重度组间比较差异有显著性（P〈0.05）。即妊娠期高血压疾病患者胎盘中MMP-9的表达显著低于正常妊娠,且随着妊娠期高血压疾病病情加重,MMP-9阳性表达呈明显减少趋势。3.TIMP-1在正常妊娠和妊娠期高血压疾病患者胎盘中的表达相比较,差异无显著性（P〉0.05）。结论MMP-9表达降低、MMP-9与TIMP-1的平衡状态改变可能与妊娠期高血压疾病发病有关,MMP-9及TIMP-1作为一对相互制约的因素在妊娠期高血压疾病发病中可能起重要作用,MMP-9有望成为妊娠期高血压疾病诊断及判断预后的新指标。     

基质金属蛋白酶在肿瘤发展过程中保护作用的研究进展

基质金属蛋白酶(MMPs)家族是细胞外蛋白水解酶,几乎可以降解所有细胞外的基质成份.普遍认为肿瘤细胞或周围基质中MMPs特异性高表达是肿瘤形成的一个重要原因,因此研究用人工合成的MMP抑制剂治疗肿瘤已成为研究领域的热点.遗憾的是在临床试验阶段该治疗方法并没有达到预期的效果.近年来通过对肿瘤初期、转移后的表达研究发现,MMPs在肿瘤发展的多个阶段起着抑制肿瘤生长的作用.     

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。     

肝素及PDGF对肾小球上皮细胞金属蛋白酶及其抑制因子表达的影响

目的 :探讨大鼠肾小球上皮细胞MMP - 2、- 9/TIMP - 1、- 2的表达情况 ,以及肝素、PDGF体外对GEC表达MMP/TIMP的影响。方法 :(1)明胶酶谱法观察肝素对上皮细胞分泌的MMP - 2、MMP - 9酶活性的影响。 (2 )应用RT -PCR半定量法观察肝素对上皮细胞表达TIMP - 1、TIMP - 2的影响。结果 :(1)明胶酶谱分析显示 :①大鼠肾小球上皮细胞能分泌MMP - 2及MMP- 9等明胶酶 ,肝素能双向调节GECMMP - 2酶活性 ,当肝素浓度为 3mg/L时 ,MMP - 2酶活性降低 ,30mg/L时MMP - 2酶活性降低更加明显 (P <0 0 1) ;但当肝素浓度为 30 0mg/L…     

基质金属蛋白酶在宫颈肿瘤中的表达及其意义

流行病学研究和实验室研究已经充分证明了,人乳头瘤病毒（HPV）的持续感染在宫颈肿瘤的形成过程中起到重要作用。而肿瘤进展的基本过程是肿瘤细胞的浸润和转移。目前许多关于此方面的研究都将焦点集中于基质金属蛋白酶（MMPs）对细胞外基质的降解上。并且研究显示MMPs（尤其是MMP-2,MMP-9）表达的上调与肿瘤的浸润、转移密切相关。本文对MMP-2、MMP-9在宫颈癌前病变组织和癌组织中的表达和活性进行综述,以寻求对宫颈肿瘤新的诊断和治疗手段。     

辛伐他汀对糖尿病高脂血症患者体内炎症水平和颈动脉斑块的影响

目的:探讨辛伐他汀对糖尿病高脂血症患者体内炎症水平和动脉斑块的影响.方法:120例2型糖尿病(DM2)合并高脂血症患者,给予控制血糖,每晚给予辛伐他汀片20mg口服,持续12周.观察患者血脂、hs-CRP、TNF-α及颈动脉斑块的变化.结果:患者经辛伐他丁治疗后血清TC、TG和LDL-C水平均较治疗前有明显降低(P<0...     

Comparison of localized versus systemic levels of Matrix metalloproteinases (MMPs), its tissue inhibitors (TIMPs) and cytokines in tuberculous and non-tuberculous pleuritis patients

The interaction of Matrix metalloproteinases (MMPs), its tissue inhibitors (TIMPs) and pro-inflammatory cytokines in response to Mycobacterium tuberculosis (MTB) infection is important to understand the immune response at the site of infection. We compared the levels of MMPs, TIMPs and cytokines in plasma (BL) and pleural fluid (PF) of tuberculosis (TB) and non tuberculosis (NTB) patients. Comparison between BL and PF showed significantly higher levels of MMP-1, TIMP-1 and -3 in TB PF; of MMP-7, -8, -9 in BL of both groups. Also, levels of MMP-1,-8,-9 and TIMP-3 were significantly higher in TB PF compared to NTB. Cytokines INF-γ, TNF-α, and IL-6 significantly increased in PF of both groups. A positive correlation of MMPs with TIMPs in TB, MMP-1 and -9 with IL-6 in TB PF and MMP-9 with IFN-γ in NTB PF was observed. This study implicates the possible usage of MMPs as bio-markers aiding diagnosis in TB pleuritis.     

Role of angiotensin II and angiotensin type-1 receptor in scorpion venom-induced cardiac and aortic tissue inflammation

Scorpion stings are mainly associated with cardiovascular disturbances that may be the cause of death. In this study, the involvement of angiotensin II (Ang II) in cardiac and aortic inflammatory response was studied. Mice were injected with Androctonus australis hector (Aah) scorpion venom (0.5 mg/kg, subcutaneously), in the presence or absence of an angiotensin converting enzyme (ACE) inhibitor, captopril (15 mg/kg/day/1 day intraperitoneally) or an angiotensin type-1 receptor (AT1R) antagonist, valsartan (15 mg/kg/day/15 days, orally). In the envenomed group, results revealed severe tissue alterations with a concomitant increase of metabolic enzymes (CK and CK-MB) in sera. An important inflammatory cell (neutrophil and eosinophil) infiltration into the heart and aorta were observed, accompanied by imbalanced redox status (NO, MDA, catalase and GSH) and high cytokine levels (IL-6 and TNF-α) in sera with the expression of MMP-2 and MMP-9 metalloproteinases. However, the blockade of the actions of AngII by the ACE inhibitor or by the AT1R antagonist prevented cardiac and aortic tissue alterations, inflammatory cell infiltration, as well as the oxidative stress generation and cytokine and metalloproteinase expression. These results suggest the involvement of AngII, through its AT1R in the inflammation induced by Aah venom, in the heart and the aorta.     

Physiological organization of immune response based on the homeostatic mechanism of matrix reprogramming: Implication in tumor and biotechnology

It is accepted that the immune system responds to pathogens with activation of antigen-independent innate and antigen-dependent adaptive immunity. However many immune events do not fit or are even inconsistent with this notion. We developed a new homeostatic model of the immune response. This model consists of four units: a sensor, a regulator, an effector and a rehabilitator. The sensor, macrophages or lymphocytes, recognize pathogenic cells and generate alarm signals. The regulator, antigen-presenting cells, Тregs and myeloid-derived suppressor cells, evaluate the signals and together with sensor cells program the effector. The effector, programmed macrophages and lymphocytes, eliminate the pathogenic cells. The rehabilitator, M2 macrophages, restrict inflammation, provide angiogenesis and reparation of tissue damage, and restore the homeostasis. We suggest the terms “immune matrix” for a biological template of immune responses to pathogens and “matrix reprogramming” for the interdependent reprogramming of different cells in the matrix. In an adequate immune response, the matrix forms a negative feedback mechanism to support the homeostasis. We defined the cellular and phenotypic composition of a tumor immune matrix. A tumor reprograms the homeostatic negative feedback mechanism of matrix into a pathogenic positive feedback mechanism. M2 macrophages play a key role in this transformation. Therefore, macrophages are an attractive target for biotechnology. Based on our hypotheses, we are developing a cell biotechnology method for creation of macrophages with a stable antitumor phenotype. We have shown that such macrophages almost doubled the survival time of mice with tumor.