核因子κB及相关基因产物的表达

背景：川芎嗪延缓肝纤维化形成的机制尚不清楚。 目的：观察川芎嗪对肿瘤坏死因子α刺激的肝星状细胞增殖及结缔组织生长因子、核因子κB及其相关基因产物白细胞介素6表达的影响。 方法：体外培养HSC-T6细胞株,取对数生长期的细胞用于实验。实验分为4组：对照组仅加入细胞;TNF-α组加入10 μg/L TNF-α;川芎嗪干预组先加入终浓度为10 μg/L的TNF-α作用30 min后,分别加入川芎嗪50,100,200,400,600, 1 000 mg/L;PDTC组先加入终浓度为10 μg/L的TNF-α作用30 min后,再加入终浓度18 μmol/L的核因子κB阻断剂PDTC。 结果与结论：MTT结果显示100,200,400,600,1 000 mg/L的川芎嗪均能抑制HSC-T6增殖,且呈剂量依赖性。免疫细胞化学染色及Western blot检测发现10 μg/L的肿瘤坏死因子α刺激后,HSC-T6细胞结缔组织生长因子、核因子κB及白细胞介素6的表达明显增多(P < 0.01或P < 0.05),200,400,600 mg/L的川芎嗪及18 μmol/L的PDTC均可明显降低肿瘤坏死因子α刺激后HSC-T6细胞结缔组织生长因子、核因子κB及白细胞介素6的表达(P < 0.01),且随着川芎嗪质量浓度的增加,抑制作用增强,PDTC的抑制作用最明显。相关性分析结果显示HSC-T6细胞结缔组织生长因子和核因子κB的表达呈正相关(r=0.980,P < 0.01)。说明川芎嗪可以抑制肝星状细胞结缔组织生长因子、核因子κB及白细胞介素6的表达,抑制肝星状细胞的增殖。     

血管损伤修复与基质金属蛋白酶★

背景：基质金属蛋白酶是一组能特异降解细胞外基质成分依赖锌的酶家族，近年来研究发现其参与了血管损伤后早期应激反应，与血管损伤后再狭窄发生相关。 目的：就基质金属蛋白酶在血管损伤中的一些生理病理过程做一综述。 方法：应用计算机检索Medline数据库、Ovid数据库、Springerlink数据库、维普数据库及中国知网数据库，纳入1990/2010发表的29篇基质金属蛋白酶与血管损伤以及药物等干预有关的文献进行总结分析。 结果与结论：心血管动脉系统在损伤后，包括经皮腔内血管成形后血管狭窄的发生率较高。基质金属蛋白酶在受损动脉的局部表达增加，通过促进内膜增厚和改变血管重构而促进血管损伤后再狭窄的发生。因此，降低血管受损局部基质金属蛋白酶表达将成为防治血管内再狭窄的一个方向。 关键词：血管损伤；血管内再狭窄；基质金属蛋白酶；基质金属蛋白酶组织抑制因子；血管组织工程     

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基质金属蛋白酶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。     

耐力运动大鼠跟腱胶原、基质金属蛋白酶1及其抑制剂1的表达

背景：胶原是肌腱细胞外基质中的主要成分,基质金属蛋白酶是降解肌腱细胞外基质蛋白的重要蛋白酶。 目的：观察12周跑台运动对大鼠跟腱胶原、胶原Ⅰ、基质金属蛋白酶1及其抑制剂1表达的影响。 方法：将20只雄性SD大鼠随机分为对照组和运动组。第1周每天运动20 min,速度由12 m/min递增至20 m/min;以后跑台速度均为20 m/min,第2周坡度为5%,时间为30 min,第3~12周坡度为10%,时间为40 min,共运动12周。对照组正常饲养。 结果与结论：末次运动后24 h取大鼠跟腱。与对照组比较,运动组大鼠跟腱前胶原Ⅰα1、基质金属蛋白酶1及其抑制剂1 mRNA的表达明显升高(P < 0.05或P < 0.01),羟脯氨酸的含量也有所增多,但与对照组比较差异无显著性意义(P > 0.05)。表明长期耐力运动可以提高跟腱中胶原的合成和降解能力。     

接受骨髓间充质干细胞移植的心肌梗死后慢性心力衰竭大鼠心肌组织 基质金属蛋白酶及抑制剂的变化

背景：Ⅰ型及Ⅲ型胶原含量与比例的变化是促使心脏几何形态改变、心肌收缩和舒展功能的重要因素，基质金属蛋白酶2及抑制剂是胶原代谢的主要调节物质。心肌梗死后心力衰竭大鼠接受骨髓干细胞移植后，心肌组织中这些指标会发生哪些变化？ 目的：观察接受骨髓干细胞移植治疗的心肌梗死后慢性心力衰竭大鼠，心肌组织中胶原含量与比例、基质金属蛋白酶2及抑制剂的变化。 设计：随机对照实验。 单位：解放军总医院老年心血管病科和北京医科大学生物化学系。 材料：实验于2004-07/2005-12在北京医科大学生物化学系周春燕实验室完成。实验动物由北京医科大学动物实验中心提供，选取4周龄清洁级雄性SD大鼠用于骨髓间充质干细胞的制备，200~250 g清洁级雌性SD大鼠14只用于心肌梗死后心力衰竭模型的制备，实验过程中对动物处置符合动物伦理学标准。 方法：采用梯度离心法与贴壁培养法分离纯化、扩增骨髓间充质干细胞。结扎雌性SD大鼠左冠状动脉制作急性心肌梗死后心力衰竭模型。造模成功4周后将14只大鼠随机分为2组：移植组大鼠梗死后心肌瘢痕区接受雄性SD大鼠来源的5×106骨髓间充质干细胞。对照组大鼠梗死后心肌瘢痕区接受等体积磷酸盐缓冲液。每组7只。 主要观察指标：移植治疗后21 d：①以苏木精-伊红染色和Masson染色评价左心室形态。②以免疫组织化学分析心肌基质金属蛋白酶2及抑制剂与瘢痕区Ⅰ型及Ⅲ型胶原的变化。③以Western杂交检测基质金属蛋白酶2及抑制剂蛋白的变化。 结果：14只大鼠均进入结果分析，无脱失值。与对照组大鼠比较，骨髓间充质干细胞移植大鼠心肌梗死瘢痕区Ⅰ型胶原增加，Ⅲ型胶原降低，心肌组织基质金属蛋白酶抑制剂表达增加，基质金属蛋白酶2表达降低，心室壁增厚，心室腔缩小，心功能增强。 结论：骨髓间充质干细胞移植心力衰竭大鼠后，基质金属蛋白酶2及抑制剂发生了动态变化，进而影响瘢痕区胶原比例重建，逆转心力衰竭心脏异常的胶原平衡。     

先天性胫骨假关节骨膜组织中基质金属蛋白酶对骨生成的影响*☆

目的: 基质金属蛋白酶在骨胚胎发育、改建及病理过程中所起的关键作用已引起人们的重视。明确基质金属蛋白酶2和基质金属蛋白酶9在先天性胫骨假关节病变处骨膜组织中的含量，探讨其与发病机制的关系。 方法：标本来自1990-01/2004-12年吉林大学第一临床医院骨关节二科收治的先天性胫骨假关节患者19例，年龄4~13岁，取材部位为假关节病变处骨膜组织；以10例正常骨膜做阴性对照，年龄10~15岁；15例胫骨闭合骨折断端周围骨膜做阳性对照。所取标本均经家属及本人同意。采用免疫组织化学方法观察上述标本骨膜组织内基质金属蛋白酶2和基质金属蛋白酶9表达。 结果：①基质金属蛋白酶2和基质金属蛋白酶9主要在血管内皮细胞胞浆中表达。②基质金属蛋白酶2和基质金属蛋白酶9在假关节病变骨膜内表达的阳性程度与创伤后骨折断端骨膜无明显差异（P > 0.05），但都明显高于正常骨膜（P < 0.05，P < 0.01）；二者在骨膜内的表达水平具有明显相关性（P < 0.01）。 结论：先天性胫骨假关节骨膜组织中基质内基质金属蛋白酶2和基质金属蛋白酶9在病理条件下表达增强影响骨生成，是形成假关节的重要原因。     

功能性矫治器引导下颌前伸后咀嚼肌中基质金属蛋白酶抑制因子及Ⅳ型胶原参与咀嚼肌的适应性变化*☆

背景：功能性矫治器引导大鼠下颌矫形治疗中，咀嚼肌也会发生适应性变化和改建，基质金属蛋白酶参与其中变化。 目的：观察功能性矫治器引导大鼠下颌前伸后咀嚼肌中基质金属蛋白酶抑制因子及其底物作用蛋白Ⅳ型胶原表达。 方法：4 周龄健康雄性SD 大鼠随机分为实验组和对照组。实验组每日白天戴矫治器10~12 h。采用免疫组织化学方法观察戴矫治器后3，7，14，21 d大鼠二腹肌前腹中基质金属蛋白酶抑制因子1，2及Ⅳ型胶原的表达。 结果与结论：实验组和对照组大鼠二腹肌前腹中基质金属蛋白酶抑制因子1，2及Ⅳ型胶原均有表达。但实验组IV型胶原、基质金属蛋白酶抑制因子1，2表达明显增强，表明功能性矫治器引导大鼠下颌前伸后咀嚼肌中 基质金属蛋白酶抑制因子1，2及Ⅳ型胶原参与了咀嚼肌的适应性变化。 关键词：咀嚼肌；基质金属蛋白酶抑制因子1；基质金属蛋白酶抑制因子2；Ⅳ型胶原；下颌前伸     

不同年龄女性血清可溶性模型基质金属蛋白酶1水平变化及对人成骨细胞凋亡的诱导

背景：前期研究表明膜型基质金属蛋白酶1在骨重建过程中可调节骨形成与骨吸收。 目的：探讨女性血清可溶性膜型基质金属蛋白酶1水平年龄变化及膜型基质金属蛋白酶1与骨密度﹑骨转换生化指标的关系。 设计、时间及地点：横断面调查,于2006-01/2007-10在中南大学湘雅二医院完成。 对象：长沙地区304名20~80岁的女性志愿者,平均年龄(49.6±14.1)岁,体质量指数(23.3±3.4) kg/m2。 方法：培养正常成人成骨细胞。留取受试者空腹静脉血,Western blot、ELISA检测血清膜型基质金属蛋白酶1可溶性蛋白水平,ELISA检测血清Ⅰ型胶原N-末端交联肽﹑骨钙素水平。测量受试者腰椎及左侧股骨颈骨密度。用重组可溶性膜型基质金属蛋白酶1蛋白干预人成骨细胞。 主要观察指标：①人成骨细胞基质金属蛋白酶1蛋白表达。②人血清可溶性膜型基质金属蛋白酶1浓度与年龄、骨密度、骨钙素、Ⅰ型胶原N-末端交联肽的关系。③人成骨细胞鉴定。④细胞凋亡检测结果。⑤重组可溶性膜型基质金属蛋白酶1蛋白诱导人成骨细胞凋亡的作用。⑥型胶原N-末端交联肽检测结果。⑧重组可溶性膜型基质金属蛋白酶1蛋白对人成骨细胞黏附功能的影响。 结果：Western blot检测到血清含有丰富的可溶性膜型基质金属蛋白酶1,血清可溶性膜型基质金属蛋白酶1与骨密度﹑Ⅰ型胶原N-末端交联肽﹑骨钙素呈负相关。重组可溶性膜型基质金属蛋白酶1蛋白促进细胞凋亡的作用呈剂量依赖性,且此作用可被乙二胺四乙酸阻断。重组可溶性活性膜型基质金属蛋白酶1蛋白抑制人成骨细胞在Ⅰ型胶原上的黏附。 结论：女性血清可溶性活性膜型基质金属蛋白酶1与骨密度﹑Ⅰ型胶原N-末端交联肽﹑骨钙素有明显相关性。重组可溶性活性膜型基质金属蛋白酶1蛋白可通过降解骨基质蛋白,诱导人成骨细胞凋亡。     

基质金属蛋白酶和胶原在创伤关节软骨组织中的表达*☆

背景：研究发现,基质金属蛋白酶和胶原参与关节软骨组织机体生理重建及病理破坏。 目的：观察膝关节骨软骨缺损及表面软骨缺损动物模型关节软骨组织中胶原及基质金属蛋白酶的表达变化。 方法：雌性SD大鼠48只随机分为3组：骨软骨缺损组在双膝关节制作骨软骨缺损模型,表面缺损组在双膝关节制作表面软骨缺损,对照组双膝关节制作关节囊切开。分别于术后4、8、12周取股骨髁标本,行苏木精-伊红染色,免疫组化检测Ⅰ型胶原、Ⅱ型胶原、基质金属蛋白酶3的表达。 结果与结论：骨软骨缺损组术后4周缺损中有少量新生组织生成,8及12周可见到纤维组织填充,修复组织细胞外基质Ⅰ型胶原免疫组化染色阳性,Ⅱ型胶原免疫组化染色阴性,关节软骨组织中基质金属蛋白酶3表达增高。表面缺损组表面软骨缺损4及8周未见修复迹象,12周可见微量纤维组织填充,细胞外基质Ⅰ型胶原免疫组化染色阳性,Ⅱ型胶原免疫组化染色阴性,术后表面缺损组关节软骨组织基质金属蛋白酶3表达增高。对照组关节软骨组织Ⅰ型胶原免疫组化染色阴性,Ⅱ型胶原免疫组化染色阳性,基质金属蛋白酶3低表达,无形态学异常改变。说明机械性损伤可以导致关节软骨细胞外基质成分发生改变,丧失其原有的生物学特性而退变,基质金属蛋白酶3在损伤后的软骨组织中表达增高,使细胞外基质的降解增加,是导致关节软骨退变的重要因素。     

体外压力刺激对大鼠“足三里”穴筋膜组织成纤维细胞合成释放基质金属蛋白酶1、基质金属蛋白酶抑制剂1、前列腺素E2和胰岛素样生长因子1的影响

背景：腧穴筋膜结缔组织成纤维细胞是针推治疗操作过程中的主要受力组织细胞之一，细胞生物学行为的调整对腧穴发挥治疗作用的功能关系密切。 目的：通过体外实验观察压力刺激对大鼠“足三里”穴筋膜组织成纤维细胞合成释放基质金属蛋白酶1、基质金属蛋白酶抑制剂1、前列腺素E2和胰岛素样生长因子1的影响。 方法：体外培养大鼠“足三里”穴筋膜组织成纤维细胞，随机分为空白对照组和压力刺激组。压力刺激组对细胞实施50kPa压力刺激，每次加力2 h，每8 h1次，共6次；空白对照组不加压。检测细胞外培养液中基质金属蛋白酶1、基质金属蛋白酶抑制剂1、前列腺素E2和胰岛素样生长因子1含量的变化，并计算基质金属蛋白酶1与基质金属蛋白酶抑制剂1比值的变化。 结果与结论：“足三里”穴筋膜组织成纤维细胞压力作用后，培养液中基质金属蛋白酶1、基质金属蛋白酶抑制剂1和前列腺素E2含量均增加(P < 0.05或0.01)，基质金属蛋白酶1与基质金属蛋白酶抑制剂1比值增大(P < 0.05)，胰岛素样生长因子1变化无显著性意义。结果证实，压力刺激对腧穴筋膜组织成纤维细胞基质金属蛋白酶1、基质金属蛋白酶抑制剂1和前列腺素E2合成释放的调节，以及对基质金属蛋白酶1与基质金属蛋白酶抑制剂1比值的提高，可能是腧穴接受针灸推拿治疗后发挥“疏经通脉”作用的细胞生物力学原理之一。     

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in perinatal asphyxia

Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) play important roles in the function of the blood–brain-barrier (BBB). We investigated the roles of MMP-9 and TIMP-1 in the pathogenesis of hypoxic–ischemic encephalopathy following perinatal asphyxia. Serum concentrations of MMP-9 and TIMP-1 were determined by ELISA in 12 neonates with perinatal asphyxia and 15 controls on the birth day and the next day. Serum MMP-9 concentrations in asphyxiated neonates with neurological sequelae (n = 5) were significantly higher than concentration in asphyxiated neonates without sequelae (n = 7) and controls on birth day (p = 0.003 and p < 0.001, respectively). The ratios of serum MMP-9/TIMP-1 on birth day in asphyxiated neonates with neurological sequelae were significantly higher than those in asphyxiated neonates without sequelae (p = 0.048). There were no significant differences in the serum MMP-9 concentrations or the ratios of MMP-9/TIMP-1 between asphyxiated neonates with and without neurological sequelae on the day after birth. Our preliminary study suggests that serum MMP-9 levels on birth day are important for predicting neurological prognosis of neonates with asphyxia.     

Matrix metalloproteinase-7 and matrix metalloproteinase-9 in pediatric multiple sclerosis

Matrix metalloproteinases and their tissue inhibitors play a key role in the pathogenesis of adult-onset multiple sclerosis, and were suggested as biomarkers of response to interferon-β, an established treatment in multiple sclerosis. However, data regarding pediatric population are scarce. We determined serum levels of matrix metalloproteinase-7, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 in children, and evaluated effects of interferon-β therapy on these measures. Serum samples from 14 children with relapsing, remitting multiple sclerosis at baseline and at month 12, and from 15 controls, were collected. Interferon-β treatment was initiated in eight patients. Mean serum matrix metalloproteinase-9 levels and matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 ratio were higher in patients compared with controls, and were reduced significantly in treated patients at month 12, but did not change in untreated patients. Mean matrix metalloproteinase-7 levels were lower in patients compared with controls, and increased significantly in the treated group, but did not change significantly in the untreated group. In pediatric multiple sclerosis, a shift in matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 balance toward proteolytic activity is evident, and interferon-β therapy demonstrates a beneficial effect on this disturbed balance.     

Matrix metalloproteinase-9 and matrix metalloproteinase-2 gene polymorphisms in multiple sclerosis

We investigated the association of matrix metalloproteinase-9 (-1562C/T, +279R/Q) and matrix metalloproteinase-2 (-1575G/A, -1306C/T) gene polymorphisms with multiple sclerosis (MS) susceptibility, gender differences and disability in 244 patients and 132 healthy subjects. A significant decrease of the -1562T allele carriers in MS patients compared to controls (Pa=0.01, Pacorr=0.05) in -1562C/T MMP-9 gene polymorphism was found, (odds ratio (OR) -0.58, 95% confidence interval (CI):0.38-0.89). Significant differences were also demonstrated between female patients and healthy females (Pa=0.01, Pacorr=0.05), (OR-0.53, 95% CI:0.32-0.86). Other polymorphisms were not associated either with MS susceptibility or with phenotype of the disease. No association with disability was found.     

Serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in non-herpetic acute limbic encephalitis

The pathogenesis of non-herpetic acute limbic encephalitis (NHALE) has been not clear. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) play important roles in the function of the blood–brain barrier. We measured the serum concentrations of MMP-9 and TIMP-1 by using enzyme-linked immunosorbent assay (ELISA) in 23 patients with NHALE in the acute and convalescent stages. Serum MMP-9 concentrations and ratios of serum MMP-9/TIMP-1 were significantly higher (1) in patients with NHALE in acute and convalescent stages than in control patients (all P < 0.001); (2) in patients with NHALE at the acute stage compared with those at the convalescent stage (P = 0.004, and P = 0.014, respectively). In contrast, serum TIMP-1 concentrations were significantly lower in patients with NHALE in the acute and convalescent stages than in control patients (both P < 0.001) but did not differ in patients with NHALE in the acute and convalescent stages. Our preliminary study suggests that the prolonged imbalance of MMP-9 and TIMP-1 is associated with the pathogenesis of NHALE.     

Expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in malignant peripheral nerve sheath tumor

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) can degrade collagen Ⅳ (the main structural ingredient of basilar membrane), and it also plays an important role in tumor vascularization, tumor cell progression, formation of metastatic focus, etc. Tissue inhibitor of metalloproteinase-1 (TIMP-1) can bind with MMP-9 to form 1∶1 compound and inhibit its activity, and can negatively regulate the tumor progression and metastasis. OBJECTIVE: To analyze the relationship of MMP-9 and TIMP-1 expressions with the pathological grade, metastasis and prognosis of malignant peripheral nerve sheath tumor (MPNST). DESIGN: An observational comparative experiment. SETTING: Heze Medical College. PARTICIPANTS: Fifty-eight surgical pathological samples, which were clearly diagnosed to be MPNST, were collected from the pathological laboratory archives in the Department of Pathology, Heze Municipal Hospital from January 1988 to December 2003. The MPNST pathological types were common tumor in 53 cases, malignant triton tumor in 2 cases, epithelial MPNST in 2 cases and MPNST with gland differentiation in 1 case. The pathological grade was grade 1 in 11 cases, grade 2 in 24 cases and grade 3 in 23 cases. Besides, the resected tumor samples of 20 patients with benign peripheral nerve tumor (10 cases of nerve sheath tumor and 10 cases of neurofibromatosis) and the normal peripheral nerves (by-products of some surgeries) of 5 patients were also collected. The samples were used with the approval of the patients. Rat-anti-human MMP-9, TIMP-1 monoclonal antibody and S-P kit were purchased from Fuzhou Maixin Biotechnology, Co.,Ltd. METHODS: The documented paraffin blocks were again prepared to sections of 5 μm. The expressions of MMP-9 and TIMP-1 in the samples were detected with mmunohistochemical S-P method. The relationships of the MPNST severity, recurrence, metastasis and survival rate with the expressions of MMP-9 and TIMP-1 were analyzed. MAIN OUTCOME MEASURES: Relationships of MMP-9 and TIMP-1 expressions with the MPNST severity and prognosis. RESULTS: ① Expressions of MMP-9 and TIMP-1 in three tissues: MMP-9 and TIMP-1 stainings were mainly observed in cytoplasm. Among the 58 MPNST patients, the MMP-9 expression was significantly higher than those in normal peripheral nerve and benign tumor (P < 0.05), while the TIMP-1 expression in MPNST was lower than those in normal peripheral nerve and benign tumor (P < 0.05). ② Relationship of MMP-9 and TIMP-1 expressions with the severity and prognosis of MPNST: The expressions of both proteins were observed in the four subtypes. The positive expression of MMP-9 in the MPNST patients of grades 2–3 was significantly higher than that in the MPNST patients of grade 1 (P < 0.05), while the expression of MMP-9 was significantly lower than that in the MPNST patients of grade 1 (P < 0.05). The metastatic rate was positively correlated with MMP-9 expression (r =1.696, P < 0.05), but negatively correlated with TIMP-1 expression (r =–2.125, P < 0.05). CONCLUSION: MMP-9 and TIMP-1 are associated with MPNST pathological grades and metastasis, and can be used as the indicators for judging the severity and prognosis of MPNST.     

基质金属蛋白酶-9与脑缺血

基质金属蛋白酶-9（matrix metalloproteinase-9．MMP-9）是一种依赖锌离子的蛋白酶，因其表达细胞众多，作用底物广泛而备受重视，与脑血管病发病过程关系密切．已成为研究热点之一。脑缺血后表达的MMP-9能降解基底膜而破坏血脑屏障（blood brain barrier，BBB），导致血管源性脑水肿和出血转化．新近的研究还发现了MMP-9在脑缺血后神经元凋亡中的作用。MMP-9抑制剂被认为是治疗缺血性脑血管病很有前景的药物，充分理解脑缺血后MMP-9的作用机制将对缺血性脑血管病冶疗有重要的启示。     

Increases in matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 mRNA after cerebral contusion and depolarisation

Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play major roles in physiological extracellular matrix turnover during normal development and in pathological processes. In brain, increases in MMP activity occur, for example, in multiple sclerosis, Alzheimer's disease, and after head trauma. We examined MMP-9 and TIMP-1, -2, and -3 in events after head trauma. A time-course study was carried out using two different rat injury models, cerebral contusion and depolarisation. Brains were analysed by RT-PCR and in situ hybridisation. We observed a distinct and time-dependent upregulation of MMP-9 and TIMP-1 mRNA in ipsilateral cortical areas. MMP-9 mRNA levels were upregulated 1 day after cerebral contusion with a peak at Day 4. Depolarisation per se, which also occurs after traumatic brain injury, lead to delayed increase of MMP-9 mRNA, 4 days post application. At Day 14, MMP-9 mRNA levels were indistinguishable from controls in both models. TIMP-1 mRNA increases were observed in both models 4 hr after injury, and increased further at Days 1 and 4. At Day 14, mRNA levels declined and were no higher than control levels. No alterations in mRNA levels were noted for TIMP-2 or -3. Our results support earlier reports on MMP-9 involvement in brain injury. It also shows a role for TIMP-1 in the mechanisms of trauma, where depolarisation could be the mechanism responsible for this upregulation.