Kim S C, Singh M, Huang J, Prestigiacomo C J, Winfree C J, Solomon R A, Connolly E S
Department of Neurological Surgery, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
Neurosurgery. 1997 Sep;41(3):642-66; discussion 646-7. doi: 10.1097/00006123-199709000-00027.
Generalized disruption of arterial wall morphological changes in patients harboring cerebral aneurysms has been documented; however, little is known regarding the pathogenesis of these changes. To explore the role of the elastolytic gelatinase, matrix metalloproteinase-9 (MMP-9), levels of this enzyme in the wall of intracranial aneurysms were compared with those in both intracranial and extracranial arteries. The tissue levels of its major inhibitor, tissue inhibitor of metalloproteinase (TIMP), were measured in these tissues as well. The activity of MMP-9 in plasma was also evaluated.
The aneurysm wall was excised from three of six patients undergoing craniotomies for aneurysm clipping. A 1-cm segment of superficial temporal artery (STA) was obtained from each of six patients. Additional STAs were obtained from six patients in the control group who were undergoing craniotomies for nonvascular disease. An intracranial artery was also obtained from the anterior temporal neocortical resection of a patient undergoing a craniotomy for mesial temporal sclerosis. MMP-9 and TIMP levels were determined via Western blot analysis. Using substrate gel Zymography, MMP-9 plasma activity was determined for a separate cohort of patients with aneurysms (n = 6) and patients in the control group (n = 6).
MMP-9 and TIMP levels in the aneurysm wall were markedly increased beyond levels in both extracranial arteries (STAs from patients with aneurysms and patients in the control group) and the intracranial artery. There were no differences in the levels of MMP-9 in the STAs of patients harboring aneurysms when compared with patients in the control group. Also, no differences were noted in plasma MMP-9 activity.
Local rather than systemic perturbations in MMP-9 levels may contribute to the matrix disruption associated with cerebral aneurysms. This local up-regulation is not the result of TIMP down-regulation. The lack of increased systemic metalloproteinase activity precludes the use of plasma MMP-9 activity as a screening tool for presymptomatic aneurysms. However, local therapeutic modulation of MMP-9 activity may help arrest aneurysm progression.
已有文献记载，患有脑动脉瘤的患者动脉壁形态发生广泛破坏；然而，对于这些变化的发病机制知之甚少。为了探究弹性蛋白酶明胶酶——基质金属蛋白酶-9（MMP-9）的作用，将颅内动脉瘤壁中该酶的水平与颅内和颅外动脉中的水平进行了比较。同时还测定了其主要抑制剂金属蛋白酶组织抑制剂（TIMP）在这些组织中的水平。此外，还评估了血浆中MMP-9的活性。
从6例接受开颅夹闭动脉瘤手术的患者中的3例切除动脉瘤壁。从6例患者中各获取一段1厘米长的颞浅动脉（STA）。另外从6例因非血管疾病接受开颅手术的对照组患者中获取STA。还从1例因内侧颞叶硬化接受开颅手术的患者的颞前新皮质切除术中获取一段颅内动脉。通过蛋白质印迹分析测定MMP-9和TIMP水平。使用底物凝胶酶谱法，对另一组动脉瘤患者（n = 6）和对照组患者（n = 6）测定血浆MMP-9活性。
动脉瘤壁中的MMP-9和TIMP水平显著高于颅外动脉（动脉瘤患者和对照组患者的STA）和颅内动脉中的水平。与对照组患者相比，患有动脉瘤的患者的STA中MMP-9水平没有差异。此外，血浆MMP-9活性也没有差异。
MMP-9水平的局部而非全身紊乱可能导致与脑动脉瘤相关的基质破坏。这种局部上调不是TIMP下调的结果。全身金属蛋白酶活性未增加，因此不能将血浆MMP-9活性用作症状前动脉瘤的筛查工具。然而，对MMP-9活性进行局部治疗性调节可能有助于阻止动脉瘤进展。
