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1.
We compared the expression of matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in bone marrow acute myelogenous leukaemia (AML) blasts and leukaemic cell lines (HEL, HL-60, K-562 and KG-1) with their expression in normal bone marrow cells. All AML samples and leukaemic cell lines tested expressed MMP-9 and/or MMP-2 mRNA and, accordingly, these gelatinases were secreted into media. Moreover, TIMP-1 and TIMP-2 mRNA and secreted proteins were demonstrated in all the AML samples. Although all the leukaemic cell lines expressed TIMP-1, the HL-60 cells also expressed TIMP-2. In contrast, normal steady-state bone marrow immature progenitor cells (CD34+ cells) did not express or secrete either MMP-2 or MMP-9, but more mature mononuclear cells from normal bone marrow expressed and secreted MMP-9. Also, normal bone marrow CD34+ cells and mononuclear cells expressed TIMP-1 and TIMP-2 mRNA, but these proteins were not detectable by reverse zymography. Furthermore, whereas bone marrow fibroblasts and endothelial cells secreted only latent MMP-2, the activated form of this enzyme was found in media conditioned by cells obtained from long-term cultures of normal and AML bone marrow adherent layers. Our finding of up-regulated production of gelatinases, TIMP-1 and TIMP-2 by leukaemic cells suggests that these proteins may be implicated in the invasive phenotype of AML.  相似文献   

2.
目的:通过比较罗格列酮和辛伐他汀对兔动脉粥样硬化基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制因子-2(TIMP-2)表达的影响,探讨罗格列酮抗动脉粥样硬化的作用机制。方法:将36只雄性新西兰兔随机分为对照组、模型组、辛伐他汀组和罗格列酮组;采用皮下注射同型半胱氨酸硫内酯及高脂饲养的方法建立兔动脉粥样硬化模型。检测血清氧化低密度脂蛋白(ox-LDL)、sCD40L水平和主动脉粥样硬化组织中MMP-2和TIMP-2的表达。结果:与对照组相比,其他3组MMP-2蛋白表达显著升高,而TIMP-2蛋白表达显著降低;与模型组比较,辛伐他汀和罗格列酮组MMP-2表达显著降低,TIMP-2表达显著增加,血清ox-LDL、sCD40L水平显著降低。辛伐他汀组和罗格列酮组比较,差异无统计学意义。结论:罗格列酮可通过下调兔主动脉粥样硬化组织中MMP-2、上调TIMP-2的表达,降低血清ox-LDL和sCD40L水平,减轻大动脉内膜的炎性反应,发挥抗动脉粥样硬化的作用。  相似文献   

3.
目的研究基质金属蛋白酶-1(MMP-1)及其抑制剂-1(TIMP-1)、肿瘤坏死因子-α(TNF-α)在溃疡性结肠炎(UC)结肠黏膜不同区域以及不同病情中的表达,探讨它们在UC发生发展中的作用和I临床意义。方法收集UC不同区域的结肠黏膜组织,分为轻、中、重三组。采用逆转录-聚合酶链反应(RT—PCR)及免疫组化检测三种因子的表达。结果MMP—1、TIMP—1、TNF-α在溃疡区的表达高于非溃疡区(P〈0.05)。MMP-1、TNF-α及TIMP-1在重型中的表达高于轻型(P〈0.05)。MMP-1/TIMP-1、TNF-α与病情严重程度相关(P〈0.05)。结论结肠黏膜中TNF-α表达升高,引起黏膜组织免疫失调,可能引起MMP-1与TIMP-1表达失衡,在UC的发生发展中起重要作用。MMP-1/TIMP-1和TNF-α可作为评价UC病情的指标。  相似文献   

4.
目的:研究基质金属蛋白酶2(MMP-2)及金属蛋白酶抑制剂-2(TIMP-2)表达在胃癌、肠癌转移及预后判断中的作用。方法:采用逆转录荧光实时定量PCR的方法检测58例结肠癌患者,52例胃癌患者外周血中MMP-2和TIMP-2 mRNA的表达水平。结果:胃癌、肠癌患者MMP-2表达均高于正常对照(P〈0.01);其中,有局部浸润、淋巴结肿大、远处脏器转移者的MMP-2 mRNA和TIMP-2/MMP-2比值与未转移者差异有统计学意义(P〈0.01);TIMP-2/MMP-2比值对判断胃癌、肠癌瘤转移的灵敏度分别为86.6%、89.2%,特异性为81.8%、83.3%。结论:基质金属蛋白酶2的表达升高与恶性肿瘤的转移密切相关,TIMP-2/MMP-2比值是恶性肿瘤转移和预后判断的良好指标。  相似文献   

5.
Due to an imbalance in the MMP:TIMP ratio determined a tissue damage in arthritis, it is hypothesized that polymorphic variations of the TIMP genes are associated with regulation of the MMP:TIMP balance. To test this hypothesis, the presence of single nucleotide polymorphisms (SNPs) located in the human TIMP-2 and TIMP-4 genes was confirmed in the Korean RA and OA patients. We performed a case-control study comprising 109 unrelated Korean OA patients, 177 unrelated Korean RA patients and 175 healthy subjects. There were statistically significant differences in the genotype distribution and allele frequencies of the C/T polymorphism of TIMP-4 gene between OA and control groups (P = 0.0002 and P = 0.001, respectively). However, no significant association between TIMP-2 polymorphisms and OA was observed. Also, no difference was observed when allele or genotype frequencies of both TIMP-2 and TIMP-4 gene polymorphisms were compared between RA and controls. We demonstrated that the C/T polymorphism which is located on the 3'-untranslational regions of the TIMP-4 gene might be associated with susceptibility to OA patients.  相似文献   

6.
目的了解慢性乙型肝炎患者肝组织和外周血清基质金属蛋白酶组织抑制物-2(TIMP-2)的表达情况,以进行对肝脏纤维化程度的评估。方法对105例慢性乙型肝炎患者肝活检组织进行肝纤维化分期。通过免疫组化技术检测患者肝组织TIMP-2的表达水平,采用ELISA法测定患者血清TIMP-2水平。结果随着慢性乙型肝炎患者肝纤维化程度的加重,肝组织TIM-2表达水平逐步上升,各期之间表达差异有统计学意义(P〈0.05);与健康对照者比,S1-S4期患者血清TIMP-2水平均升高(P〈0.05),除S1与S2期之间无显著性差异外,其余各期之间TIMP-2水平有统计学差异。结论肝组织和外周血TIMP-2表达水平可以较好地反映肝脏的纤维化程度。  相似文献   

7.
兔主动脉球囊损伤后MMP-2和TIMP-2 mRNA的动态变化   总被引:2,自引:0,他引:2  
目的 :探讨基质金属蛋白酶 2 (MMP 2 )、基质金属蛋白酶组织抑制因子 2 (TIMP 2 )核糖核酸 (mR NA)在主动脉球囊损伤后的改变及可能作用。方法 :在兔腹主动脉球囊损伤的模型上 ,应用RT PCR的方法 ,观察MMP 2、TIMP 2mRNA在球囊损伤后不同时间的表达情况。结果 :MMP 2mRNA在球囊损伤后第 1天表达开始升高 ,第 7天达高峰。TIMP 2mRNA球囊损伤后第 1天表达开始逐渐升高 ,第 2 8天达高峰。结论 :MMP 2mRNA在球囊损伤后表达第 7天达高峰 ,在再狭窄早期平滑肌细胞的迁移与增殖中起重要作用 ;TIMP 2mRNA球囊损伤后表达第 2 8天达高峰 ,可能与再狭窄中、后期新生内膜形成及血管重塑有关。  相似文献   

8.
目的 观察基质金属蛋白酶-9(MMP-9)及组织型蛋白酶抑制剂-1(TIMP-1)在慢阻肺继发肺间质纤维化(PIFCOPD)大鼠肺组织中的变化,评价其与PIF-COPD的病理变化及发病机制的相关性.方法 雄性大鼠24只,随机分为正常对照组(1组),21天(2组)和42天(3组)模型组.以烟熏联合气管内滴注脂多糖建立PIF-COPD模型.免疫组化法检测肺组织中MMP-9及TIMP-1水平.结果 MMP-9和TIMP-1在1组有少量表达;在2和3组MMP-9为0.1970±0.0017和0.2414 ±0.0017;TIMP-1为0.1265 ±0.0018和0.2171 ±0.0023(与l组相比P<0.05)水平逐渐增高且与肺间质纤维化的严重程度成正相关.结论 MMP-9及TIMP-1的水平与PIF-COPD的发病机制及病程有关.  相似文献   

9.
目的探讨气体信号分子二氧化硫(SO2)对急性心肌梗死大鼠心肌纤维化的作用及其对基质金属蛋白酶(MMP)-3/MMPs抑制剂(TIMP)-1蛋白表达的影响。方法将40只健康雄性成年SD大鼠随机分为正常对照(Control)组、模型[异丙肾上腺素(Iso)]组、SO2干预(Iso+SO2)组、SO2对照(SO2)组。首先构建急性心肌梗死大鼠模型组,Iso组和Iso+SO2组予以持续2 d腹腔注射Iso 50 mg/(kg·d),Control组及SO2组大鼠则腹腔注射等量生理盐水,行心电图及肌钙蛋白检测,确定造模成功后,Iso+SO2组和SO2组大鼠腹腔注射亚硫酸钠(Na 2SO 3)/亚硫酸氢钠(NaHSO 3)溶液(0.54±0.18)mmol/(kg·d),Control组及Iso组则腹腔注射等量生理盐水;持续4 w后,将大鼠处死,通过Masson染色检测心肌胶原沉积情况,用Western印迹对大鼠心肌组织MMP-3和TIMP-1蛋白表达水平变化进行检测。结果与Control组相比,Iso组心肌组织间可见明显胶原纤维沉积,MMP-3蛋白表达显著上升(P<0.05),TIMP-1蛋白表达显著下降(P<0.05)。Iso+SO2组与Iso组相比,大鼠心肌组织可见胶原纤维沉积减少,MMP-3蛋白表达水平下降(P<0.05),TIMP-1表达水平明显上升(P<0.05)。结论SO2可能通过调控MMP-3/TIMP-1改善Iso诱导的急性心肌梗死大鼠的心肌纤维化。  相似文献   

10.
This is the first study to describe the role of MMP-2 and MMP-9 in Hodgkin's disease. Strong MMP-2 expression correlated with a favorable prognosis, while MMP-9 expression showed a tendency toward an adverse outcome. MMP-9 expression correlated with B symptoms and decreased new vessel formation. MMP-2 expression was associated with the nodular sclerosis subtype, and its expression was most pronounced in the vicinity of sclerosis. Neither of the gelatinases nor the extent of neovascularization correlated with tumor stage, the occurrence of bulky disease, or extranodal infiltrates. Together, these findings imply that the adverse role of MMP-9 may be associated with the controlling of immunological processes but not the invasion probabilities or neovascularization of the tumor. The favorable prognostic value of MMP-2 is surprising in view of the role of MMPs in solid tumors. This, however, may be linked to the basic biological differences of hematological malignancies vs. other tumors.  相似文献   

11.
OBJECTIVES: The present study was carried out to clarify the role of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and the extent of neovascularization in the clinicopathologic behavior of non-Hodgkin's lymphomas. METHODS: Paraffin-embedded histologic sections from 57 patients with aggressive non-Hodgkin's lymphomas were stained with MMP-2, MMP-9, TIMP-1, and factor VIII antibodies to correlate the expression of these markers to the clinical disease characteristics. RESULTS: Strong MMP-9 staining was found to be an adverse prognostic factor among patients with aggressive B-cell lymphomas, the probabilities for 5-yr disease-free survival being 73%, 63%, 50%, and 0% in patients with grades 0, 1, 2, and 3 staining, respectively. Among the patients with strong (grades 2 and 3) MMP-9 staining, however, positivity for TIMP-1 indicated a trend toward a more favorable prognosis. TIMP-1 expression also correlated with the immunoblastic and anaplastic lymphoma subtypes. The expression of the proteins for MMP-2 and factor VIII had no independent prognostic role. None of the study parameters correlated with disease stage, the occurrence of extranodal infiltrates, the occurrence of bulky tumor, or the IPI scores. CONCLUSIONS: Positivity for MMP-9 immunoreactive protein is an independent sign of an unfavorable prognosis in non-Hodgkin's lymphomas. This is not mediated through influences in tumor dissemination or neovascularization indicating it to carry other important biological functions.  相似文献   

12.
目的 了解TIMP-1和TIMP-2在肝硬化患者肝组织中的表达状态,探讨TIMP-1和TIMP-2在肝硬化发病机理中的作用。方法 以抗TIMP-1和TIMP-2单克隆抗体(McAb)为试剂,采用免疫组织化学法检测肝硬化患者肝组织中TIMP-1和TIMP-2相关抗原的表达。结果 30例肝硬化病人肝组织中TIMP-1和TIMP-2相关抗原表达的阳性率为100%,TIMP-1阳性的肝组织中TIMP-2亦为阳性,且TIMP-1强度高于TIMP-2,而正常肝组织无一例表达阳性。TIMP-1和TIMP-2抗原表达阳性信号主要位于肝细胞胞浆中,未见细胞核表达。结论 肝硬化患者肝细胞中存在TIMP-1和TIMP-2相关抗原表达,TIMP-1和TIMP-2与肝病的进展相关,它通过抑制MMPs的活性,使得ECM降解减少而导致肝纤维化,以致肝硬化。  相似文献   

13.
目的:探讨TIMP-3和RASSF1A在大肠癌发生发展中的作用及与临床病理特征之间的关系,并且研究TIMP-3和RASSF1A之间的相关性.方法:应用免疫组织化学法检测大肠癌组织,大肠癌旁组织及正常大肠黏膜组织中TIMP-3和RASSF1A蛋白的表达量并结合患者的年龄、性别、分化程度、淋巴结转移等临床病理因素进行综合分析.采用Spearman等级相关分析TIMP-3和RASSF1A之间的相关性.结果:在正常大肠黏膜、癌旁和腺癌中TIMP-3的阳性率分别为90.0%、70.0%和16.7%,RASSF1A阳性率分别为83.3%、63.3%和23.3%.大肠癌中TIMP-3和RASSF1A的表达量与淋巴结转移(P<0.05;P<0.01)、浸润深度(P<0.05;P<0.01)及分化程度(P<0.05;P<0.05)有关.运用Spearman等级相关分析,TIMP-3和RASSF1A的表达呈正相关(r=0.256,P<0.05).结论:在大肠癌中TIMP-3和RASSF1A具有明显相关性,TIMP-3和RASSF1A的表达下调可能与大肠癌的发生有关,可以作为鉴别大肠良恶性肿瘤的指标.  相似文献   

14.
We analysed age and sex-specific trends in the incidence of Hodgkin's lymphoma in Denmark, Sweden, Norway, and Finland during 1978-97. The incidence of Hodgkin's lymphoma decreased significantly in all age groups above 40 years; there was a significant increase in incidence among adolescents and young adults. This increase occurred primarily for Hodgkin's lymphoma of the nodular sclerosis subtype. These observations emphasise the need to identify risk factors for Hodgkin's lymphoma in the young.  相似文献   

15.
AIM: To investigate DNA ploidy and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma and to explore the mechanism of invasion and metastasis of gastric carcinoma. METHODS: Immunohistochemical methods were used to detect the expressions of MMP-9, TIMP-2, and E-cadherin in 156 cases, including 99 cases of gastric carcinoma, 16 cases of adjacent noncancerous mucosa, 16 cases of distant metastases and 25 cases of metastatic lymph node (LN) from gastric carcinoma. Flow cytometry DNA ploidy and S-phase fraction (SPF) analysis were performed on 57 cases, including 47 cases of gastric cancer, 6 cases of adjacent noncancerous mucosa, and 4 cases of distant metastatic cancer. RESULTS: The expression of MMP-9 was significantly correlated with Lauren's classification, Borrmann's classification, LN metastasis, tumor metastasis, and TNM stage, as well as depth of invasion (all P<0.05). The positive rate was lower in noncarcinoma than in carcinoma (31.3% vs66.7%, P<0.01). The expression of TIMP-2 was significantly correlated with Borrmann's classification, LN metastasis, and the depth of invasion (all P<0.05), The expression of E-cadherin was significantly correlated with differentiation, Lauren's classification, Borrmann's classification, and LN metastasis, as well as the depth of invasion (P<0,01 or P<0.05). E-cadherin was less expressed in carcinoma than in noncarcinoma (42.4% vs87.5%, P<0.01). There was a positive correlation between MMP-9 and TIMP-2 and a negative correlation between MMP-9 and E-cadherin, but no correlation between TIMP-2 and E-cadherin. Also there was a positive correlation between DNA aneuploid rate and differentiation and LN metastasis. SPF that was higher than 15% was positively correlated with tumor size, differentiation and LN metastasis. And there was a significant difference between carcinoma and noncarcinoma in DNA aneuploid rate and SPF. CONCLUSION: With tumor progression and development of heterogeneity, the abnormal expressions of MMP-9, TIMP-2, and E-cadherin or DNA aneuploid rate or high SPF gradually increases, suggesting that they play a crucial role in gastric carcinoma progression.  相似文献   

16.
咳喘宁对支气管哮喘大鼠气道重塑及MMP-9、TIMP-1的影响   总被引:2,自引:0,他引:2  
目的 观察咳喘宁对支气管哮喘大鼠气道形态学和基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂-1(TIMP-1)的影响.方法 40只SD大鼠随机分为正常组、模型组、咳喘宁高、低剂量组(27 和13.5 g生药/kg体重)、桂龙咳喘宁胶囊对照组(0.41 g/kg体重),每组8只.除正常组外以卵蛋白致敏并吸入激发法制备大鼠支气管哮喘模型,各治疗组均从第1次哮喘激发开始(造模第3周)至处死前每天灌胃给药,激发并给药4 w后处死大鼠,取肺组织HE染色,彩色图像分析仪测量支气管管壁厚度、平滑肌厚度,采用ELISA双抗体夹心法测定肺组织MMP-9、TIMP-1含量.结果 与正常组比较,模型组大鼠支气管管壁和平滑肌厚度、肺组织MMP-9、TIMP-1含量及二者比值明显增加(P<0.01);与模型组比较,各治疗组均可显著降低支气管管壁和平滑肌厚度(P<0.01),降低肺组织MMP-9、TIMP-1含量以及二者比值(P<0.05或P<0.01);且咳喘宁高、低剂量组优于桂龙咳喘宁胶囊组(P<0.05或P<0.01).结论咳喘宁可通过降低肺组织MMP-9和TIMP-1含量,调节二者比值,抑制支气管哮喘大鼠气道壁增厚和平滑肌增生肥大,从而抑制支气管哮喘大鼠气道重塑.  相似文献   

17.

OBJECTIVES:

Adiponectin, an adipocyte-specific protein, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in arteriosclerosis and plaque disruption. The present study was designed to elucidate the relationship of adiponectin and the ratio of MMP-9/TIMP-1 and their effects on the stability of plaque in acute coronary syndrome (ACS).

METHODS:

The concentrations of adiponectin, MMP-9, TIMP-1 and interleukin-10 were analyzed using ELISA in 56 consecutive unselected patients divided into two groups, stable angina (n=13) and ACS (n=43), and were compared with 19 healthy control subjects. The 56 patients were also angiographically studied and divided into two groups, simple lesion (n=22) and complex lesion (n=34), based on coronary plaque morphology.

RESULTS:

The ratio of MMP-9/TIMP-1 showed significantly higher values in the ACS group compared with the control group (0.22±0.10 versus 0.11±0.03; P<0.001). Adiponectin was negatively correlated with the ratio of MMP-9/TIMP-1 (r=–0.332; P=0.008) and positively correlated with interleukin-10 (r=0.651; P=0.001). Multivariate logistic regression analysis showed that adiponectin (P=0.046) and MMP-9/TIMP-1 (P=0.044) are independent predictors for ACS, and MMP-9/TIMP-1 (P=0.013) is an independent predictor for complex lesion morphology plaques.

CONCLUSION:

In the present study, it was found that adiponectin has a negative relationship with the ratio of MMP-9/TIMP-1 in patients with ACS, and that the ratio of MMP-9/TIMP-1 is an independent predictor of the stability of atherosclerotic plaque and the severity of coronary atherosclerosis.  相似文献   

18.
目的探讨基质金属蛋白酶9(MMP9)及其抑制剂(TIMP1)在子宫内膜异位症(EMs)发生发展过程中的作用。方法收集50例EMs患者的异位内膜组织标本和20例在位内膜组织标本,采用免疫组化方法分别检测MMP9、TIMP1在两组组织中的表达。结果MMP9、TIMP1在异位内膜中多呈阳性或强阳性表达,但两者表达程度不同,前者随美国生育协会(rAFS)分期增高表达上调,后者则随rAFS分期增高表达下调,两者相比较差异具有显著性意义(P<005)。正常对照组的在位内膜中多呈弱阳性表达或无表达,两组比较差异极具显著意义(P<001)。结论MMP9/TIMP1表达失衡在EMs发生发展过程中可能有着重要作用。  相似文献   

19.
目的从TGF-α、TGF-β配体成员(TGF-β1、TGF-β2、TGF-β3)、TIMP-1、TIMP-2、MMP-2筛选在非小细胞肺癌(NSCLC)中mRNA水平异常表达的细胞因子,并探讨其临床意义。方法实时定量PCR法检测NSCLC组织和毗邻正常组织中TGF-α、TGF-β1、TGF-β2、TGF-β3、TIMP-1、TIMP-2、MMP-2 mRNA表达量,并研究其与患者临床病理特征之间的关系。结果 NSCLC组织中TGF-α、TGF-β1表达量均明显高于正常组织(0.046 vs 0.005,P0.01;16.91 vs 11.76,P=0.04),TIMP-2水平降低(25.23 vs 207.85,P=0.02),而NSCLC中MMP-2/TIMP-2显著高于正常肺组织(0.77 vs 0.02,P=0.04)。III-IV期NSCLC组织的TGF-α水平高于III期(0.06 vs 0.02,P0.01)。有淋巴结转移组TGF-β1水平高于无淋巴结转移组(17.70 vs 10.00,P0.01)。鳞癌组织中TIMP-2水平低于腺癌组织(20.06 vs 33.51,P=0.02),无淋巴结转移组TIMP-2水平高于有淋巴结转移组(30.02 vs 20.56,P=0.03)。结论 TGF-α与NSCLC进展密切相关;TGF-β1在NSCLC的发生、发展、侵袭转移中发挥重要作用;MMP-2/TIMP-2可能是较敏感的肿瘤生物学指标,且TIMP-2与NSCLC侵袭转移相关,相对高表达的TIMP-2可能提示腺癌。  相似文献   

20.
目的探讨基质金属蛋白酶-9(MMP-9)和组织金属蛋白酶抑制剂-1(TIMP-1)在食管鳞癌中的表达及其临床意义。方法用免疫组化和Western blot法分别检测41例食管鳞癌患者的癌及相应正常组织中MMP-9和TIMP-1的表达变化。结果食管鳞癌组织中MMP-9阳性表达率与食管癌淋巴结及静脉转移有关;MMP-9的阳性表达率与表达量均显著高于TIMP-1;MMP-9和TIMP-1的表达呈负相关。结论MMP-9与食管鳞癌的侵袭转移有关,其机制可能与食管鳞癌组织中的MMP-9/TIMP-1平衡失调有关;MMP-9与TIMP-1联合检测有助于食管鳞癌生物学行为的判断。  相似文献   

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