Bruno G, Todor R, Lewis I, Chyatte D
Cerebrovascular Research Laboratory, The Cleveland Clinic Foundation, Ohio 44195, USA.
J Neurosurg. 1998 Sep;89(3):431-40. doi: 10.3171/jns.1998.89.3.0431.
The occurrence of cerebral aneurysms has been linked to alterations in the extracellular matrix and to matrix-degrading proteases. The purpose of the present study was to determine whether active extracellular matrix remodeling occurs within cerebral aneurysms.
Aneurysm tissue was collected from 23 patients (two of whom had a ruptured aneurysm and 21 of whom had an unruptured aneurysm) and compared with 11 control basilar arteries harvested at autopsy. Active proteinases capable of gelatin lysis were identified by performing in situ zymography in the presence and absence of a metalloproteinase inhibitor (ethylenediamine tetraacetic acid) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride). Immunohistochemical analysis was used to localize plasmin, tissue-type (t)-plasminogen activator (PA), urokinase-type (u)-PA, membranetype (MT1)-matrix metalloproteinase (MMP), MMP-2, MMP-9, and tenascin. Focal areas of gelatin lysis occurred in most cerebral aneurysm tissue samples (17 of 21), but rarely in control arteries (two of 11) (p = 0.002). Both serine proteinases and MMPs contributed to gelatin lysis; however, the MMPs were the predominant enzyme family. Plasmin (p = 0.04) and MT1-MMP (p = 0.04) were expressed in the aneurysm tissue but were unusual in control tissue. The MMP-2 was also expressed more commonly in aneurysm than in control tissue (p = 0.07). The MMP-9 and t-PA were expressed in both groups; however, different staining patterns were observed between aneurysm and control tissue. Tenascin staining was commonly present in both groups, whereas u-PA staining was rarely present.
Aneurysm tissue demonstrates increased proteolytic activity capable of lysing gelatin and increased expression of plasmin, MT1-MMP, and MMP-2 when compared with normal cerebral arteries. This activity may contribute to focal degradation of the vascular extracellular matrix and may be related to aneurysm formation and growth.
脑动脉瘤的发生与细胞外基质的改变以及基质降解蛋白酶有关。本研究的目的是确定脑动脉瘤内是否发生活跃的细胞外基质重塑。
从23例患者（其中2例为破裂动脉瘤，21例为未破裂动脉瘤）收集动脉瘤组织，并与11例尸检时获取的对照基底动脉进行比较。通过在存在和不存在金属蛋白酶抑制剂（乙二胺四乙酸）和丝氨酸蛋白酶抑制剂（苯甲基磺酰氟）的情况下进行原位酶谱分析，鉴定能够溶解明胶的活性蛋白酶。免疫组织化学分析用于定位纤溶酶、组织型（t）-纤溶酶原激活物（PA）、尿激酶型（u）-PA、膜型（MT1）-基质金属蛋白酶（MMP）、MMP-2、MMP-9和腱生蛋白。大多数脑动脉瘤组织样本（21例中的17例）出现局灶性明胶溶解区域，但对照动脉中很少见（11例中的2例）（p = 0.002）。丝氨酸蛋白酶和MMP均促成明胶溶解；然而，MMP是主要的酶家族。纤溶酶（p = 0.04）和MT1-MMP（p = 0.04）在动脉瘤组织中表达，但在对照组织中不常见。MMP-2在动脉瘤中的表达也比对照组织更常见（p = 0.07）。MMP-9和t-PA在两组中均有表达；然而，在动脉瘤和对照组织之间观察到不同的染色模式。腱生蛋白染色在两组中均常见，而u-PA染色很少见。
与正常脑动脉相比，动脉瘤组织显示出能够溶解明胶的蛋白水解活性增加以及纤溶酶、MT1-MMP和MMP-2的表达增加。这种活性可能有助于血管细胞外基质的局灶性降解，并且可能与动脉瘤的形成和生长有关。
