RNA干扰技术对小鼠巨噬细胞基质金属蛋白酶9表达的抑制

目的：构建基质金属蛋白酶9靶向的RNA干扰质粒载体，观察其对小鼠巨噬细胞基质金属蛋白酶9基因表达的沉默作用。 方法：实验于2004-11／2005—07在哈尔滨医科大学第一临床医学院中心实验室完成。设计能转录小发卡结构RNA的DNA序列，并与psiSTRIKE^TM质粒载体连接，构建受控于人RNA聚合酶Ⅲ启动子U6的真核表达载体，以脂质体法将重组质粒导人小鼠巨噬细胞内，采用Invitrogen公司Lipofectamne^TM2000转染试剂进行转染。实验分为实验组、阴性对照组和空白对照组。实验组每孔分别加入4μL脂质体和psiSTRIKE^TM／基质金属蛋白酶9重组质粒2μg；阴性对照组只加2μL Lipofectamne^TM2000转染试剂；空白对照组则不加任何干扰因素。分别于转染前、转染24，48，72h后用反转录-聚合酶链反应和免疫组织化学技术检测基质金属蛋白酶9mRNA及蛋白水平的表达情况。 结果：①成功构建靶向基质金属蛋白酶9基因发夹状RNA干扰质粒载体。②实验组转染重组质粒24，48，72h后阳性细胞率与转染前相比逐渐减少（分别为70％，42％，32％，99％，P〈0．01），而阴性对照组和空白对照组则差异无显著性意义。③转染小鼠巨噬细胞后，基质金属蛋白酶9mRNA蛋白表达下调。 结论：构建的RNA干扰真核表达载体能明显抑制基质金属蛋白酶9mRNA及蛋白的表达，提示通过减少动脉粥样硬化斑块细胞外基质的降解，来稳定动脉粥样硬化斑块，在基因治疗方向为斑块稳定进行了新的尝试。     

RNA干扰技术对小鼠巨噬细胞基质金属蛋白酶9表达的抑制

目的:构建基质金属蛋白酶9靶向的RNA干扰质粒载体,观察其对小鼠巨噬细胞基质金属蛋白酶9基因表达的沉默作用。方法:实验于2004-11/2005-07在哈尔滨医科大学第一临床医学院中心实验室完成。设计能转录小发卡结构RNA的DNA序列,并与psiSTRIKETM质粒载体连接,构建受控于人RNA聚合酶Ⅲ启动子U6的真核表达载体,以脂质体法将重组质粒导入小鼠巨噬细胞内,采用Invitrogen公司LipofectamneTM2000转染试剂进行转染。实验分为实验组、阴性对照组和空白对照组。实验组每孔分别加入4μL脂质体和psiSTRIKETM/基质金属蛋白酶9重组质粒2μg;阴性对照组只加2μLLipofectamneTM2000转染试剂;空白对照组则不加任何干扰因素。分别于转染前、转染24,48,72h后用反转录-聚合酶链反应和免疫组织化学技术检测基质金属蛋白酶9mRNA及蛋白水平的表达情况。结果:①成功构建靶向基质金属蛋白酶9基因发夹状RNA干扰质粒载体。②实验组转染重组质粒24,48,72h后阳性细胞率与转染前相比逐渐减少(分别为70%,42%,32%,99%,P<0.01),而阴性对照组和空白对照组则差异无显著性意义。③转染小鼠巨噬细胞后,基质金属蛋白酶9mRNA蛋白表达下调。结论:构建的RNA干扰真核表达载体能明显抑制基质金属蛋白酶9mRNA及蛋白的表达,提示通过减少动脉粥样硬化斑块细胞外基质的降解,来稳定动脉粥样硬化斑块,在基因治疗方向为斑块稳定进行了新的尝试。     

Corticotropin-releasing hormone enhances the invasiveness and migration of Ishikawa cells, possibly by increasing matrix metalloproteinase-2 and matrix metalloproteinase-9

Corticotropin-releasing hormone (CRH), synthesized in the hypothalamus, is also produced at several extrahypothalamic sites and in normal endometrial cells. CRH exerts antiproliferative activity on oestrogen-dependent tumour cell lines (Ishikawa cells and breast cancer cells) via the CRH receptor-1. This study investigated the potential role of CRH as a factor affecting endometrial migration and invasion in Ishikawa cells, and the possible mechanisms involved in this process. Increasing concentrations of CRH (1, 10 and 100 nM) significantly reduced the proliferation of Ishikawa cells but increased the invasiveness these cells compared with the control group. All three concentrations of CRH significantly increased matrix metalloproteinase (MMP)-2 and MMP-9 levels in Ishikawa cells. In conclusion, CRH inhibited the growth of Ishikawa cells but enhanced their invasiveness, possibly by increasing MMP-2 and MMP-9 levels. These findings suggest that CRH might induce invasion and migration by upregulating MMP-2 and MMP-9 in endometrial cancer.     

ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis

Matrix metalloproteinase-1 (MMP-1), or interstitial collagenase, has been hypothesized to contribute to the progression of the human atherosclerotic lesions by digesting the fibrillar collagens of the neointimal ECM. The apolipoprotein E knockout (apoE0) mouse model develops complex atherosclerotic lesions, but mice do not possess a homologue for MMP-1. To provide an in vivo evaluation of the role of MMP-1 in atherogenesis, we created a transgenic mouse model that expresses this enzyme specifically in the macrophage, under the control of the scavenger receptor A (SCAV) enhancer/promoter. The MMP-1 transgenic mice were crossed into the apoE0 background and fed an atherogenic diet for 16-25 weeks. Surprisingly, the transgenic mice demonstrated decreased lesion size compared with control littermates. The lesions of the transgenic animals were less extensive and immature, with fewer cellular layers and a diminished content of fibrillar collagen. There was no evidence of plaque rupture. Our data suggest that remodeling of the neointimal extracellular matrix by MMP-1 is beneficial in the progression of lesions.     

脑出血灶周脑组织MMP-2和MMP-9的表达

目的观察急性脑出血患者灶周脑组织基质金属蛋白酶-2（MMP-2）、MMP-9的表达及其意义。方法选择42例采用外科手术治疗的急性脑出血患者破碎脑组织病理标本;另选30例脑外伤患者出血灶周破损脑组织作为对照。用免疫组化法测定脑组织MMP-2、MMP-9阳性细胞表达情况。结果两组患者脑组织MMP-9和MMP-2阳性细胞表达明显升高。42例急性脑出血早期患者灶周脑组织MMP-9、MMP-2阳性细胞表达分别为39例和37例;而30例脑外伤出血患者脑组织MMP-9、MMP-2阳性细胞表达分别为28例和27例,两组比较差异均无显著性（P均〉0.05）。结论MMP-2和MMP-9参与了人类急性脑出血脑水肿的形成。     

Excessive matrix metalloproteinase-9 in the plasma of community-acquired pneumonia

BACKGROUND: It has been shown that matrix metalloproteinase-9 (MMP-9) is involved in the pathogenesis of various pulmonary inflammatory diseases. We determined the MMP-9 concentration in the plasma of community-acquired pneumonia (CAP) patients before and after antibiotic treatment. METHODS: Gelatin zymography and ELISA analysis were used to measure MMP-9 activity and MMP-9 level, respectively, in 35 control subjects and 46 CAP patients. RESULTS: WBC counts, neutrophils, MMP-9 activity and MMP-9 level were significantly higher in CAP patients compared with that of control subjects (P<0.001), while MMP-9 activity and MMP-9 level were returned to normal after the antibiotic treatment (P<0.001). In addition, MMP-9 level correlated positively with WBC counts and neutrophils number both before and after the antibiotic treatment. CONCLUSIONS: MMP-9 may play an important role in the pathogenesis of CAP with a positive correlation with the number of neutrophils.     

Lipoprotein lipase secretion by human monocyte-derived macrophages.

Human monocyte-derived macrophages in culture produced lipoprotein lipase. Although freshly isolated blood monocytes did not secrete much lipase activity, 1 d in culture was sufficient to trigger measureable enzyme production. During 3 wk in culture, maximal activity was attained after 7 d. At all times, the culture medium contained more enzyme activity than did a serum-heparin eluate or a detergent extract of the cell layer. The lipase activity was stimulated by serum and was inhibited by preincubation with antiserum to bovine lipoprotein lipase or when assayed at a high salt concentration. Furthermore, the enzyme bound to a heparin-Sepharose affinity column at physiological ionic strength. Cells cultured from a subject with primary lipoprotein lipase deficiency secreted no detectable enzyme. Since macrophages are prominent components of atherosclerotic lesions in man, their ability to synthesize and secrete lipoprotein lipase may be important to atherogenesis.     

Protease inhibitor treatments reveal specific involvement of matrix metalloproteinase-9 in human adipocyte differentiation

We previously showed that human and murine 3T3-F442A preadipocytes produced and released matrix metalloproteinases (MMPs) 2 and 9 and that a treatment by MMP inhibitors resulted in the blockade of murine fat cell adipose conversion. In parallel, investigators reported that other protease inhibitors, the human immunodeficiency virus (HIV) protease inhibitors (PIs) involved in lipodystrophy in humans, also reduced the adipocyte differentiation process of several murine cell lines. The present work was performed to define the effects of MMP inhibitors and HIV-PIs on the human adipocyte differentiation process, to clarify the involvement of MMPs in the control of human adipogenesis, and to determine whether HIV-PIs interact with MMPs in the control of this process. The effect of two MMP inhibitor and four HIV-PI treatments on the differentiation of primary culture human preadipocytes, as well as the putative relationships between HIV-PIs and MMP-2 and -9 expression, release, or activity were investigated. We showed that MMP inhibitors and HIV-PIs reduced the human adipocyte differentiation process as assessed by the decrease of cell protein and/or triglyceride contents and expression of fatty acid binding protein and hormone-sensitive lipase, two adipocyte markers. Unlike MMP inhibitors, HIV-PIs were devoid of any effect per se on recombinant MMP-2 and 9 activities but reduced the expression and release of MMP-9 by human preadipocytes. Thus, the present study indicates that the modulation of the extracellular matrix components through the production and/or activity of MMPs, and, more precisely, MMP-9 might be a key factor in the regulation of human adipose tissue development.     

口腔疣状癌基质金属蛋白酶-2、基质金属蛋白酶-9和金属蛋白酶组织抑制因子-2的表达及其相关性的研究

目的:研究口腔疣状癌中基质金属蛋白酶(MMP)-2、MMP-9及金属蛋白酶组织抑制因子(TIMP-2)的表达.探讨其在口腔疣状癌发生发展过程中的作用和意义.方法:取25例口腔疣状癌,10例正常口腔黏膜,25例口腔鳞癌(高、低分化鳞癌各为15、10例),应用免疫组织化学法检测上述标本中MMP-2、MMP-9及,TIMP-2的表达和分布.结果:正常口腔黏膜组织TIMP-2为阴性表达:MMP-2、MMP-9的阳性表达率分别为10.00%、20.00%.口腔疣状癌MMP-2阳性表达率为28.00%.MMP-9阳性表达率为44.00%,TIMP-2阳性表达率为72.00%.口腔疣状癌、口腔高分化鳞癌、口腔低分化鳞癌MMP-2、MMP-9、TIMP-2表达均高于正常口腔黏膜(P<0.05).结论:在口腔疣状癌,口腔高分化鳞癌、口腔低分化鳞癌中.MMP-2与MMP-9的阳性表达率呈正相关,与TIMP-2呈负相关;相关分析发现,MMP-2、MMP-9和TIMP-2的袁达两两相关,同时3者的表达可能单独或共同参与.     

基质金属蛋白酶9在腹主动脉瘤体组织中的高度表达及其致病作用

背景：人腹主动脉瘤的发病机制十分复杂，目前尚未完全明了，基质金属蛋白酶9在腹主动脉瘤形成与发展过程中可能具有促进作用。目的：通过检测基质金属蛋白酶9在人腹主动脉瘤组织中的定位表达，评价基质金属蛋白酶9在腹主动脉瘤发病机制中的作用及临床意义。设计：随机对照、重复测量设计。单位：德国科隆大学医院血管外科中心。对象：组织标本选择2002—05／2003—02德国科隆大学医院血管外科中心手术治疗的腹主动脉瘤患者20例，男18例，女2例；年龄56-81岁；随机选择下肢动脉硬化闭塞症血管旁路手术患者15例及其他非血管手术患者10例为对照。方法：同样条件下切取上述患者腹主动脉瘤瘤体组织、下肢动脉硬化闭塞症硬化动脉管壁和正常动脉管壁组织。采用免疫组织化学技术，检测了基质金属蛋白酶9在20例腹主动脉瘤瘤体组织中的定位表达，并与15例下肢动脉硬化闭塞性疾病的病变管壁、1O例非血管疾病（正常动脉）管壁组织中的基质金属蛋白酶-组织学表达进行对照研究。主要观察指标：基质金属蛋白酶9在3种不同动脉血管条件下的组织定位表达结果及表达水平。结果：①腹主动脉瘤动脉壁中富含大量基质金属蛋白酶9颗粒，其阳性表达率达95％（19／20）。②正常动脉管壁组织未检测到基质金属蛋白酶9的表达；下肢动脉硬化病变血管壁内可见散在分布的基质金属蛋白酶9阳性颗粒，其阳性表达率为26．7％（4／15）。③与正常动脉管壁和下肢动脉硬化血管壁相比较，基质金属蛋白酶9在腹主动脉瘤瘤体组织中的表达具有显著性差异（P〈0．01）。结论：腹主动脉瘤体组织中基质金属蛋白酶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．在腹主动脉瘤的发病机制中具有重要作用。     

基质金属蛋白酶9在腹主动脉瘤体组织中的高度表达及其致病作用

背景:人腹主动脉瘤的发病机制十分复杂,目前尚未完全明了,基质金属蛋白酶9在腹主动脉瘤形成与发展过程中可能具有促进作用。目的:通过检测基质金属蛋白酶9在人腹主动脉瘤组织中的定位表达,评价基质金属蛋白酶9在腹主动脉瘤发病机制中的作用及临床意义。设计:随机对照、重复测量设计。单位:德国科隆大学医院血管外科中心。对象:组织标本选择2002-05/2003-02德国科隆大学医院血管外科中心手术治疗的腹主动脉瘤患者20例,男18例,女2例;年龄56～81岁;随机选择下肢动脉硬化闭塞症血管旁路手术患者15例及其他非血管手术患者10例为对照。方法:同样条件下切取上述患者腹主动脉瘤瘤体组织、下肢动脉硬化闭塞症硬化动脉管壁和正常动脉管壁组织。采用免疫组织化学技术,检测了基质金属蛋白酶9在20例腹主动脉瘤瘤体组织中的定位表达,并与15例下肢动脉硬化闭塞性疾病的病变管壁、10例非血管疾病(正常动脉)管壁组织中的基质金属蛋白酶-组织学表达进行对照研究。主要观察指标:基质金属蛋白酶9在3种不同动脉血管条件下的组织定位表达结果及表达水平。结果:①腹主动脉瘤动脉壁中富含大量基质金属蛋白酶9颗粒,其阳性表达率达95%(19/20)。②正常动脉管壁组织未检测到基质金属蛋白酶9的表达;下肢动脉硬化病变血管壁内可见散在分布的基质金属蛋白酶9阳性颗粒,其阳性表达率为26.7%(4/15)。③与正常动脉管壁和下肢动脉硬化血管壁相比较,基质金属蛋白酶9在腹主动脉瘤瘤体组织中的表达具有显著性差异(P<0.01)。结论:腹主动脉瘤体组织中基质金属蛋白酶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,在腹主动脉瘤的发病机制中具有重要作用。     

Effect of erythromycin on matrix metalloproteinase-9 and cell migration

Erythromycin (EM) has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases such as diffuse panbronchiolitis. To investigate the mechanism of this anti-inflammatory effect, we studied the relationship between the concentration of EM and matrix metalloproteinase-9 (MMP-9) activity, which is important in cell migration. We showed that EM suppressed the gelatinolytic activity of U937 cell-derived MMP-9 by using gelatin zymography, showed that expressions of MMP-9 protein and MMP-9 mRNA were down-regulated by EM in a dose-dependent manner, and showed that U937 migration was also suppressed by EM. We also demonstrated that EM treatment suppressed the gelatinolytic activity of MMP-9 in spleen macrophages. These findings suggest that the suppressive effect of EM on MMP-9 activity is one of the anti-inflammatory mechanisms that inhibit the migration of inflammatory cells into the inflammatory site.     

蜂胶黄酮对人脐静脉内皮细胞基质金属蛋白酶9的影响

背景:研究表明,基质金属蛋白酶9与动脉粥样硬化斑块的稳定性有关,蜂胶黄酮具有抗动脉粥样硬化的作用.目的:拟证实蜂胶黄酮对人脐静脉内皮细胞摹质金属蛋白酶9表达的影响.设计、时间及地点:对比观察.实验于2008-01/08在山东泰山医学院生命科学研究所完成.材料:蜂胶黄酮由泰山医学院生命科学研究所实验室提取;出生1 h内新生儿脐带由山东泰安市中心医院提供,产妇知情同意.方法:进行人脐静脉内皮细胞的体外培养和鉴定.按四甲基偶氮唑盐实验筛选的浓度,分别加入25,50,100,200 mg/L不同剂量的蜂胶黄酮处理细胞24 h,以空白组做对照.主要观察指标:免疫细胞化学染色和ELISA法测定蜂胶黄酮对基质金属蛋白酶9表达的影响.结果:不同剂量的蜂胶黄酮作用人脐静脉内皮细胞24 h后均能明显抑制细胞基质金属蛋白酶9的表达,并且随着浓度的升高抑制作用明显增强.结论:蜂胶黄酮能明显降低人脐静脉内皮细胞基质金属蛋白酶9的表达.     

血管内皮生长因子对佐剂性关节炎滑膜细胞基质金属蛋白酶3及基质金属蛋白酶9表达的影响

目的:观察血管内皮生长因子对佐剂性关节炎滑膜细胞质金属蛋白酶3及质金属蛋白酶9表达的影响,并探讨其意义。方法:实验于2006-02/12在桂林医学院实验中心完成。①实验材料:清洁级8周龄雄性Wistar大鼠6只,血管内皮生长因子为Peprotech EC LTD公司产品,基质金属蛋白酶3(扩增369bp)上游引物、下游引物,基质金属蛋白酶9(扩增405bp)上游引物、下游引物均购自晶美公司。②实验干预:先用弗氏完全佐剂造Wistar大鼠模型;造模20d后取Wistar大鼠右后足滑膜细胞进行原代培养。③实验分组:实验分为血管内皮生长因子组:取P2代细胞接种于6孔培养板,分别加入终浓度为5,25,50μg/L血管内皮生长因子;对照组:不加血管内皮生长因子。④实验评估:取病理切片观察滑膜细胞形态学改变;采用半定量反转录聚合酶链反应检测Wistar大鼠佐剂性关节炎滑膜细胞基质金属蛋白酶3及基质金属蛋白酶9的m-RNA表达。结果:①培养细胞的形态学观察:原代培养14d滑膜细胞从组织块边缘逸出,21d密集生长开始传代;传代细胞48h可明显分辨出树突样细胞、巨噬细胞样细胞和成纤维细胞样细胞;传至21代,细胞生长及特性稳定。②病理切片:滑膜组织有中性粒细胞、单核细胞、淋巴细胞浸润,滑膜细胞增生、排列紊乱,纤维素渗出,胶原纤维沉着,纤维素样坏死,呈滑膜炎表现。③基质金属蛋白酶3、基质金属蛋白酶9的mRNA表达:对照组基质金属蛋白酶3mRNA表达相对灰度值与血管内皮生长因子终浓度5,25,50μg/L组比较,差异有显著性意义(0.32±0.03,0.77±0.06,1.12±0.12,1.59±0.02,P<0.05);对照组基质金属蛋白酶9mRNA表达相对灰度值与血管内皮生长因子终浓度5,25,50μg/L组比较,差异有显著性意义(0.47±0.07,0.50±0.10,0.91±0.10,1.31±0.06,P<0.05);基质金属蛋白酶3和基质金属蛋白酶9mRNA表达随血管内皮生长因子浓度的加大表达增加。结论:血管内皮生长因子以剂量递增的方式对体外培养的佐剂性关节炎滑膜细胞基质金属蛋白酶3及基质金属蛋白酶9的表达有促进作用。     

基质金属蛋白酶-2,9及细胞外基质金属蛋白酶诱导因子与骨肉瘤患者性别、年龄、预后的关系

目的检测基质金属蛋白酶-2(MatrixMetalloProteinase-2,MMP-2)、基质金属蛋白酶-9(MatrixMetalloProteinase-9,MMP-9)及细胞外基质金属蛋白酶诱导因子(ExtracellularMatrixMetalloProteinaseInducer,EMMPRIN)在骨肉瘤组织中的表达,并判断其与骨肉瘤患者性别、年龄、肿瘤的部位、病理分型和复发、转移的关系,寻找有利于保肢治疗的良好时机。方法收集1996-05/2003-05临床病理资料完整、获得随访的骨肉瘤患者60例,对其手术标本中具有诊断意义的部位进行免疫组织化学染色(S-P法),观察MMP-2,9及EMMPRIN在骨肉瘤中的表达,并对其与患者性别、年龄、肿瘤的部位、病理分型和复发、转移的关系进行统计学分析。结果在60例骨肉瘤标本中,MMP-2阳性率77%(46/60),MMP-9阳性率78%(47/60),EMMPRIN阳性率72%(43/60),三者与患者的性别、年龄、肿瘤的部位、病理分型均无显著性相关关系(P>0.05)。MMP-2,9的表达与肿瘤的复发有显著性相关关系(P<0.05),但和肿瘤的转移无显著性相关关系(P>0.05)。EMMPRIN的表达不但与肿瘤的复发有显著性相关关系(P<0.05),而且和肿瘤的转移也有显著性相关关系(P<0.05)。EMMPRIN与MMP-2的相关系数为0.626(P<0.05),与MMP-9的相关系数为0.504(P<0.05)。结论EMMPRIN的表达与MMP-2,9的表达呈正相关,与     

急性冠状动脉综合征患者血清基质金属蛋白酶-9及其抑制物水平变化

目的:观察不同类型冠心病患者血清基质金属蛋白酶-9、组织金属蛋白酶抑制物-1水平的变化,进一步了解血清基质金属蛋白酶-9及组织金属蛋白酶抑制物-1在冠状动脉粥样硬化发生发展中的作用及临床意义.方法:采用酶联免疫吸附法测定60例冠心病患者(急性冠状动脉综合征患者30例、稳定性心绞痛患者30例)、30例非冠心病患者(对照组)血清基质金属蛋白酶-9,组织金属蛋白酶抑制物-1的水平.结果:急性冠状动脉综合征组血清基质金属蛋白酶-9水平高于稳定性心绞痛组及对照组(P<0.01),而血清组织金属蛋白酶抑制物-1水平低于稳定性心绞痛组及对照组(P<0.01).稳定性心绞痛组血清基质金属蛋白酶-9水平高于对照组(P<0.01),血清组织金属蛋白酶抑制物-1水平低于对照组(P<0.01).急性冠状动脉综合征患者治疗后血清基质金属蛋白酶-9水平低于治疗前,组织金属蛋白酶抑制物-1高于治疗前(P<0.01).结论:血清基质金属蛋白酶-9水平增高及组织金属蛋白酶抑制物-1水平降低与粥样斑块破裂相关,可作为判断粥样斑块不稳定的血清学指标.血清基质金属蛋白酶-9水平增高及组织金属蛋白酶抑制物-1水平降低有助于评价冠状动脉病变的程度及冠心痛患者的预后.     

新生儿机械通气患者血清MMP-9,TIMP-1测定及研究

目的探讨新生儿机械通气患者肺损伤与患者血清(MMP-9)及其组织抑制因子(TIMP-1)的关系。方法32例机械通气的新生儿患者组与对照组分别均测定血清MMP-9,TIMP-1浓度,并相互进行比较。两组数据比较均用非配对资料的t检验。结果机械通气新生儿患者组血清MMP-9水平较未机械通气新生儿患者组高(P<0.05,而机械通气新生儿患者组血清TIMP-1水平与未机械通气新生儿患者组相比差异无显著性(P>0.05)。结论新生儿机械通气后血清中的MMPs/TIMPs失衡,导致MMPs活性增强,过度增强的MMPs活性导致了细胞外基质的降解,可能造成基底膜受损。加速了炎性反应,与新生儿呼吸机相关性肺损伤(VILI)的发生相关联。     

Expression of matrix metalloproteinase-9 in mononuclear cells of hyperhomocysteinaemic subjects

Atherosclerotic plaque instability and rupture requires extracellular matrix modification, a complex process regulated by matrix metalloproteinases (MMPs). We hypothesized that homocysteine's atherogenic effects may involve MMP-mediated mechanisms. Our results showed the following: (i) Compared with healthy control subjects (n = 9), patients with hyperhomocysteinaemia (n = 9) had elevated mRNA levels of MMP-9 and tissue inhibitors of metalloproteinases-1 (TIMP-1) in freshly isolated peripheral blood mononuclear cells (PBMCs), which were positively correlated with homocysteine and negatively correlated with folate and vitamin B12 levels. (ii) Peripheral blood mononuclear cells obtained from these patients released markedly enhanced the amount of MMP-9 upon oxidized LDL (oxLDL) stimulation, whereas no such enhancing effect was seen in cells from healthy controls. (iii) During folic acid 6 weeks' treatment, normalization of homocysteine levels was accompanied by a significant reduction in mRNA levels of MMP-9 and TIMP-1 in PBMCs, as well as a marked reduction in oxLDL-stimulated release of MMP enzyme activity. These novel findings may suggest that homocysteine exerts its atherogenic effect in part by elevating levels and activity of MMPs, which in turn may enhance matrix degradation, potentially promoting atherogenesis and plaque instability. Moreover, our findings suggest that folic acid supplementation may down-regulate these inappropriate responses in these patients.     

慢性阻塞性肺疾病患者急性加重期血清基质金属蛋白酶抑制剂及基质金属蛋白酶9浓度与肺功能变化的关系

目的探讨慢性阻塞性肺疾病急性加重期(AECOPD)患者血清MMP-9、TIMP-1浓度的变化及其与肺功能变化的关系。方法应用酶联免疫吸附(ELISA)方法检测58例AECOPD患者和30名健康人血清中MMP-9、TIMP-1浓度。结果AECOPD患者血清MMP-9、TIMP-1浓度[(128.89±115.84)ng/mL、(228.28±107.133)ng/mL]明显高于对照组[(30.65±18.43)ng/mL、(133.69±41.41)ng/mL,P<0.01]。AECOPD组和对照组血清MMP-9、TIMP-1浓度与FEV1占预计值%具有负相关性(r=-0.591、-0.651,P<0.01);AECOPD组和对照组血清MMP-9、TIMP-1浓度与FEV1/FVC%具有负相关性(r=-0.558、-0.653,P<0.01);MMP-9/TIMP-1比率与FEV1占预计值%及FEV1/FVC%具有负相关性(r=-0.373、-0.356,P<0.05)。结论MMP-9、TIMP-1是引起肺功能下降很重要的因素。     

脑胶质瘤基质金属蛋白酶9表达与磁共振成像特征的相关性

目的 探讨脑胶质瘤MMP-9表达与肿瘤病理分级、磁共振成像(MRI)特征的关系.方法 31例胶质瘤患者分为低级别组(Ⅰ、Ⅱ级)20例、高级别组(Ⅲ、Ⅳ级)11例, 术前均接受MR平扫及增强扫描.以免疫组化染色观察MMP-9表达,并与MRI瘤周水肿指数(EI)、强化程度(EP)及肿瘤最大直径相比较.结果 高级别胶质瘤组MMP-9表达、EI、EP、肿瘤最大直径显著高于低级别胶质瘤组(t=6.312、4.405、6.286和5.026,P均＜0.05).MMP-9表达与肿瘤EI、EP、最大直径呈正相关(r=0.516,0.554和0.676,P＜0.05).MMP-9表达在边界清晰和不清晰肿瘤间差异无统计学意义(t=0.906,P＞0.05),而在信号均匀与不均匀肿瘤间差异有统计学意义(t=2.637,P＜0.05).结论 MMP-9表达与脑胶质瘤侵袭性密切相关,MRI所示瘤周水肿、肿瘤强化程度、肿瘤最大直径、信号均匀与否反映MMP-9表达,可作为判断肿瘤恶性的指标.