冠状动脉介入治疗对肿瘤坏死因子a和基质金属蛋白酶-9水平的影响

目的观察经冠状动脉介入治疗（PCI）治疗对肿瘤坏死因子α（TNF-α）及基质金属蛋白酶-9（MMP-9）的影响。方法纳入存在单支病变经PCI治疗的冠心病患者60例,同期经冠状动脉造影证实冠状动脉正常者30例作为对照组。分析两组冠心病危险因素的合并比例,采用酶联免疫吸附法分别检测入选患者冠状动脉介入治疗前后TNF-α和MMP-9水平并进行组间比较。结果①有冠状动脉狭窄需行PCI治疗患者存在冠心病危险因素的比例高于对照组;②PCI组患者术后血浆TNF-α显著高于术前[（19.89±5.41）ng/mLvs.（15.78±5.34）ng/ml,P〈0.01],对照组冠状动脉造影术后TNF-α与术前相比差异无统计学意义[（13.76±5.54）ng/mLvs.（12.48±5.12）ng/mL,P〉0.05];③PCI组患者术后血浆MMP-9显著高于术前[（21.97±5.93）mg/Lvs.（18.65±5.72）mg/L,P〈0.01],对照组冠脉造影术后MMP-9与术前相比差异无统计学意义[（16.21±5.33）mg/Lvs.（15.31±5.21）mg/L,P〉0.05]。结论需PCI治疗的患者冠心病危险因素高于无冠脉狭窄者,冠脉介入治疗较冠脉造影可造成冠心病患者血浆TNF-α及MMP-9水平明显升高,可能与术后支架再狭窄有关。     

复方丹参对冠心病基质金属蛋白酶-9和肿瘤坏死因子-α的影响

目的：观察复方丹参滴丸治疗稳定型心绞痛（SAP）患者4周后血清基质金属蛋白酶-9（MMP-9）和肿瘤坏死因子α（TNF-α）的变化，以了解复方丹参滴丸治疗对斑块稳定性的影响。方法：60例SAP患者被分为复方丹参滴丸治疗组和常规治疗组，测定治疗前后MMP-9和TNF-α水平。结果：复方丹参滴丸治疗组MMP-9和TNF-α水平较治疗前及对照组明显降低（P均〈0.01）。结论：复方丹参滴丸治疗可明显降低稳定型心绞痛患者炎症因子MMP-9和TNF-α水平，有利于稳定动脉粥样硬化斑块。     

冠心病心绞痛患者血浆肿瘤坏死因子α和基质金属蛋白酶-9变化及其临床意义

目的探讨肿瘤坏死因子α(TNF-α)及基质金属蛋白酶-9(MMP-9)在冠心病心绞痛发病机制中的作用。方法选择冠状动脉造影确诊的心绞痛患者80例,分为稳定型心绞痛(SAP)组39例,不稳定型心绞痛(UAP)组41例,30例冠状动脉造影正常者作为对照组。采用酶联免疫吸附(ELISA)法检测血浆TNF-α、MMP-9水平。结果 UAP组血浆TNF-α、MMP-9水平为(26.95±6.02)ng/L、(23.79±4.67)mg/L,显著高于SAP组的(23.64±5.87)ng/L和(19.56±4.51)mg/L(P<0.05),两组TNF-α、MMP-9均明显高于对照组[(16.53±5.45)ng/L、(15.45±4.28)mg/L(P<0.05)]。结论炎症反应可能参与冠心病的发病过程,血浆TNF-α与MMP-9对预测冠心病心绞痛存在和发展有重要临床意义。     

大鼠脑缺血再灌注后肿瘤坏死因子-α及基质金属蛋白酶-9的表达

目的　观察大鼠局灶性脑缺血再灌注后肿瘤坏死因子 α(TNF α)和基质金属蛋白酶 9(MMP 9)表达的情况 ,探讨二者在缺血再灌注炎症反应和脑水肿形成中的作用。方法　用雄性SD大鼠 72只 ,随机分为正常对照组、假手术组和缺血再灌注组。线栓法建立大鼠局灶性脑缺血再灌注模型 ,分别观察再灌注后 3、6、2 4、4 8h、5dTNF α和MMP 9表达的情况 ,并测定脑组织含水量。结果　缺血再灌注组TNF α、MMP 9的阳性细胞数明显增多 ,再灌注 6hTNF α的阳性细胞数达高峰 ,再灌注 2 4hMMP 9的阳性细胞数明显增高 ,持续至再灌注 5d。脑含水量于再灌注 2 4、4 8h显著增高与MMP 9表达趋势一致。结论　TNF α是缺血再灌注的触发因素 ,诱导MMP 9表达 ,参与再灌注的病理过程。     

肝癌组织基质金属蛋白酶9与肿瘤坏死因子受体1的关系

目的研究基质金属蛋白酶9（MMP-9）与肝癌细胞可溶性肿瘤坏死因子受体1（sTNFR1）表达的关系。方法通过RT-PCR和明胶酶谱法检测MMP-9在肝癌组织和癌旁组织中的表达情况,同时应用ELISA法检测血清中sTNFR1的水平。结果①RT-PCR示肝癌组织中MMP-9 mRNA明显高于癌旁组织（P〈0．05）;②明胶酶谱示肝癌组织中MMP-9活性明显高于癌旁组织;③肝癌患者血液中sTNFR1明显升高（P〈0．05）。结论MMP-9可能诱导肝癌细胞表面sTNFR1脱落,使肿瘤细胞逃过自身免疫系统的杀伤机制,这可能与肝癌侵袭转移密切相关。     

肿瘤坏死因子α刺激培养的人肝星状细胞表达基质金属蛋白酶的研究

目的　了解肿瘤坏死因子 (TNF)α对培养的人肝星状细胞表达基质金属蛋白酶 (MMP)的影响。方法　分离、培养人肝星状细胞 ,用于TNFα刺激。用酶联免疫吸附试验检测不同时间培养上清液中的MMP-1、MMP-2和MMP-3浓度。结果　受TNFα刺激的肝星状细胞表达MMP-1、MMP-2和MMP-3水平呈逐渐上升趋势 ,从刺激后 2 0h开始显著增加 :MMP-1水平 2 8h >2 4h >2 0h >4～ 16h(P <0 .0 0 1) ;MMP 2水平 2 8h >2 4h >2 0h(P <0 .0 0 1) >4～ 16h(P <0 .0 5 ) ;MMP 3水平 2 8h >2 4h(P <0 .0 1) ,2 4h >2 0h >4～ 16h(P <0 .0 5 )。TNF α刺激后肝星状细胞产生的MMP 1和MMP 2平均浓度 8h时已高于对照组 (P <0 .0 5 ) ,2 0h后显著高于对照组 (P <0 .0 1～ 0 .0 0 1)。而MMP 3平均浓度在 4～ 16h与对照组相比差异无显著性 (P >0 .0 5 ) ,2 0h后才显著高于对照组 (P <0 .0 1)。结论　TNFα可刺激星状细胞表达MMP-1、MMP-2和MMP-3 ,其表达水平随刺激时间的延长呈逐渐增加趋势     

肿瘤坏死因子-α与基质金属蛋白酶9在心力衰竭中的变化及药物干预的影响

目的：探讨血浆肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶9(MMP_9)在心力衰竭(心衰)中变化以及福辛普利干预的影响。方法：测定59例心衰患者(心衰组)以及20例健康者(正常对照组)血浆 TNF-α、MMP_9及脑钠肽(BNP)的浓度,经胸超声心动图检查,测出左心室舒张末内径、左心室射血分数及左心室短轴缩短率,将心衰组随机分为27例常规治疗者和32例加用福辛普利者,1个月后再测定上述指标。结果：心衰组血浆 TNF-α、MMP_9及 BNP 的浓度均高于正常对照组,且随心功能恶化,增加越显著(P 均＜0.05)。心衰组血浆 TNF-α、MMP_9浓度分别与 BNP 水平及左心室舒张末内径呈正相关,而与左心室射血分数及左心室短轴缩短率呈显著负相关,并且 TNF-α与 MMP+9呈显著正相关(P 均＜0.05)。福辛普利能改善心功能,降低上述细胞因子的浓度 (P 均＜0.05)。结论：心衰患者血浆 TNF-α、MMP_9与 BNP 水平三者密切相关,TNF-α和基质金属蛋白酶(MMPs)在心衰的发展中起重要作用,福辛普利能改善心功能,也降低血浆中 TNF-α和 MMPs 水平。     

胃肠安方对胃癌基质金属蛋白酶9及基质金属蛋白酶抑制因子1/2蛋白表达的影响

[目的]观察胃肠安方对人胃癌裸鼠原位移植瘤转移的抑制作用及其对基质金属蛋白酶9 (matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶抑制因子(matrix metalloproteinases tissue inhibitor,TIMP)-1、TIMP-2蛋白表达的影响.[方法]建立裸小鼠胃原位癌模型,分为胃肠安方组及模型组,观察裸小鼠胃癌种植后肿瘤转移灶情况以及与肿瘤生长与转移密切相关的MMP-9、TIMP-1、TIMP-2的影响.[结果]胃肠安方能够抑制胃癌生长与转移,与模型组比较,差异具有统计学意义(P＜0.05).胃肠安方组MMP-9蛋白阳性表达明显弱于模型组,TIMP-1及TIMP-2蛋白阳性表达明显强于模型组.[结论]胃肠安方具有抑制人胃癌裸鼠原位移植瘤转移作用,其抑制胃癌转移的部分作用机制与抑制MMP-9蛋白表达及上调TIMP-1、TIMP-2蛋白表达有关.     

基质金属蛋白酶-1、转录调节因子Ets-1与肿瘤关系的研究进展

在肿瘤发生发展过程中,侵袭与转移是其最主要的生物学特征之一,也是肿瘤药物的作用靶点之一。在此过程中,基质金属蛋白酶（MMPs）在降解基底膜（BM）和细胞外基质（ECM）中发挥重要作用,可促进肿瘤侵袭和转移。Ets-1作为转录调节因子和肿瘤的发生发展也密切相关。本文仅对MMPs家族中的MMP-1及其关联因子Ets-1与肿瘤关系的研究进展进行简要综述。     

肝纤维化基质金属蛋白酶-26/基质金属蛋白酶抑制因子-1 mRNA的表达

基质金属蛋白酶（MMPs）是一组能降解细胞外基质（ECM）的酶，该家族的一些酶是迄今为止已发现的惟一能分解纤维类胶原的酶类，MMP-26是MMPs家族的一个新成员，又称endometase或matrilysin-2，MMP-26可能参与一系列与组织重建有关的事件。基质金属蛋白酶组织抑制因子（TIMP）是一组能特异性抑制MMPs活性的低分子蛋白质，     

Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas

AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.     

Claudin 1 mediates tumor necrosis factor alpha-induced cell migration in human gastric cancer cells

AIM: To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha (TNF-α)-induced gene expression in human gastric adenocarcinoma cells.METHODS: Knockdown experiments were conducted with claudin 1 small interfering RNA (siRNA), and the effects on the cell cycle, apoptosis, migration and invasion were analyzed in human gastric adenocarcinoma MKN28 cells. The gene expression profiles of cells were analyzed by microarray and bioinformatics.RESULTS: The knockdown of claudin 1 significantly inhibited cell proliferation, migration and invasion, and increased apoptosis. Microarray analysis identified 245 genes whose expression levels were altered by the knockdown of claudin 1. Pathway analysis showed that the top-ranked molecular and cellular function was the cellular movement related pathway, which involved MMP7, TNF-SF10, TGFBR1, and CCL2. Furthermore, TNF- and nuclear frctor-κB were the top-ranked upstream regulators related to claudin 1. TNF-α treatment increased claudin 1 expression and cell migration in MKN28 cells. Microarray analysis indicated that the depletion of claudin 1 inhibited 80% of the TNF-α-induced mRNA expression changes. Further, TNF-α did not enhance cell migration in the claudin 1 siRNA transfected cells.CONCLUSION: These results suggest that claudin 1 is an important messenger that regulates TNF-α-induced gene expression and migration in gastric cancer cells. A deeper understanding of these cellular processes may be helpful in establishing new therapeutic strategies for gastric cancer.     

A tumor necrosis factor binding protein is present in human biological fluids

Tumor necrosis factor (TNF) possesses both beneficial and toxic bioactivities. Mechanisms may operate to counteract harmful effects. We have identified a TNF binding protein (TNF-BP), which shows increased levels in serum and urine of patients on regular hemodialysis treatment (RDT). TNF-BP inhibited the specific binding of human recombinant TNF (rTNF) to its cell surface receptor. Results from gel chromatography demonstrated the presence in serum and urine of a macromolecule with an apparent molecular weight of 50,000, which formed a complex with rTNF. A 62-fold purification of TNF-BP from urine of patients on RDT was achieved by ion exchange chromatography and gel chromatography. Partially purified TNF-BP reduced the growth inhibitory effect of rTNF on a susceptible leukemia cell line. TNF-BP may act as a regulator of the biological activity of TNF and could have beneficial effects in certain inflammatory conditions.     

Study of tumor necrosis factor receptor in the inflammatory bowel disease

Ulcerative colitis(UC) and Crohn’s disease(CD) are part of Inflammatory Bowel Diseases(IBD) and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-α is a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients wit...     

Prognostic significance of p53 and matrix metalloproteinase-9 expression in follicular lymphoma

Objectives: p53 mutations and high protein expression are associated with adverse prognosis in several lymphoma subtypes. Matrix metalloproteinase‐9 (MMP‐9) has also been found to correlate with poor survival in all lymphomas studied. The data concerning the clinical role of protein expression of p53 or gelatinases and their inhibitors in follicular lymphoma are rare. The purpose of this study was to evaluate the prognostic and clinical implications of the immunoreactive proteins p53, MMP‐2, MMP‐9, tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1) and TIMP‐2 in follicular lymphoma. Methods: The material consisted of 67 patients with primarily non‐transformed follicular lymphoma. Diagnostic lymph node tissue sections of patients were stained by immunohistochemical method using specific monoclonal antibodies. Results: p53 over‐expression was detected in 8 (12%) out of 67 cases. p53 over‐expression correlated with high grade (P = 0.011), bulky tumour (P = 0.031) and forthcoming transformation (P = 0.001). It also correlated with poor overall (P = 0.001) and cause‐specific survival (P = 0.010) in multivariate analysis and had a strong inverse correlation with time to transformation (P < 0.001). MMP‐2, MMP‐9 and TIMP‐2 expression correlated with high grade. MMP‐9 positivity in centroblasts correlated with good chemotherapy response (P = 0.019), but it was not prognostic for survival. MMP‐2, TIMP‐1 or TIMP‐2 did not associate with survival, either. Conclusions: In this study, p53 over‐expression predicted both transformation to diffuse large B‐cell lymphoma and poorer overall and cause‐specific survival of patients with follicular lymphoma. Expression of gelatinases or their inhibitors did not have any significant correlations with prognosis, although MMP‐9 predicted a good response to first‐line chemotherapy.     

Serum matrix metalloproteinase-1 in patients with chronic viral hepatitis

BACKGROUND AND AIMS: Previously we found that serum matrix metalloproteinase (MMP)-1 activity decreased with progression of chronic liver disease. Our objectives in the present study were to observe the change in the serum MMP-1 protein concentration using recently developed specific enzyme immunoassays for MMP-1 and MMP-1 complexed with tissue inhibitor of metalloproteinases (TIMP)-1 and to elucidate the clinical usefulness of the serum MMP-1 test in chronic viral hepatitis. We measured the serum concentrations of MMP-1 and MMP-1/TIMP-1 complex using these immunoassays in 64 patients with histologically characterized chronic viral hepatitis. RESULTS: Serum MMP-1 concentration was inversely related to the histological severity of chronic hepatitis (P< 0.0001). It was closely associated with the histological degree of periportal necrosis (P< 0.0001), intralobular necrosis (P< 0.005), portal inflammation (P<0.0001) and liver fibrosis (P< 0.05). The serum concentration of MMP-1/TIMP-1 complex was also related to the histological severity of chronic hepatitis (P< 0.0001). It was associated with the degree of portal inflammation (P< 0.05), but not with the degree of periportal necrosis, intralobular necrosis or liver fibrosis. As serum MMP-1 level was closely associated with the histological degree of necroinflammation, we examined the ability of the serum MMP-1 test to differentiate active and inactive forms of hepatitis with a receiver operating curve. The results were compared with those of serum procollagen type III N-peptide (PIIINP) test. We found that the serum MMP-1 test was superior to the serum PIIINP test in assessing liver necroinflammation. CONCLUSIONS: In addition to the previously reported changes in enzyme activity, MMP-1 proteins in serum decreased during histological progression of chronic hepatitis. The serum MMP-1 test may be useful clinically to differentiate active and inactive types of hepatitis in patients with chronic viral hepatitis.