Montaner J, Alvarez-Sabín J, Molina C, Anglés A, Abilleira S, Arenillas J, González M A, Monasterio J
Cerebrovascular Unit, Hemostasia Research Unit, Vall d'Hebron Hospital, Barcelona, Spain.
Stroke. 2001 Aug;32(8):1759-66. doi: 10.1161/01.str.32.8.1759.
Uncontrolled expression of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation. In animal models of cerebral ischemia, the expression of MMP-2 and MMP-9 was significantly increased. However, their role in human stroke in vivo remains unknown. Therefore, we sought to determine the temporal profile of MMP expression in patients with acute ischemic stroke and to investigate its relationship to stroke severity, location of arterial occlusion, and total infarct volume.
Serial MMP-2 and MMP-9 determinations were made in 39 patients with cardioembolic strokes that involved the middle cerebral artery territory by means of enzyme-linked immunosorbent assay. Blood samples, transcranial Doppler recordings, and National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at 12, 24, and 48 hours after stroke onset. Infarct volume was measured with CT scanning at 48 hours.
No correlation was found between MMP-2 and NIHSS score at any time point, although a close relation appeared between mean MMP-9 and final NIHSS score (r=0.486, P=0.002). MMP-9 value was the only factor associated with the final NIHSS score in the multiple logistic regression model (OR 4.54, 95% CI 1.5 to 13.75). A cut-point of MMP-9 142.18 ng/mL had a positive predictive value of 94.4% to assess a patient's NIHSS (<8 or >/=8) by the end of the study. Final MMP-2 and MMP-9 levels were significantly lower when recanalization occurred (528+/-144.3 versus 681.4+/-239.2 ng/mL, P=0.031 for MMP-2; 110.2+/-100.9 versus 244.8+/-130 ng/mL, P=0.004 for MMP-9). A positive correlation was found between mean MMP-9 and infarct volume (r=0.385, P=0.022).
MMPs are involved in the acute phase of human ischemic stroke. MMP-9 levels are associated with neurological deficit, middle cerebral artery occlusion, and infarct volume.
基质金属蛋白酶（MMPs）的失控表达可导致组织损伤和炎症。在脑缺血动物模型中，MMP-2和MMP-9的表达显著增加。然而，它们在人类缺血性脑卒中活体中的作用仍不清楚。因此，我们试图确定急性缺血性脑卒中患者MMP表达的时间变化情况，并研究其与脑卒中严重程度、动脉闭塞部位及梗死总体积的关系。
采用酶联免疫吸附测定法，对39例累及大脑中动脉区域的心源性脑栓塞性脑卒中患者进行MMP-2和MMP-9的系列测定。在基线以及脑卒中发作后12、24和48小时采集血样、经颅多普勒记录及美国国立卫生研究院卒中量表（NIHSS）评分。在48小时时用CT扫描测量梗死体积。
在任何时间点，MMP-2与NIHSS评分之间均未发现相关性，尽管平均MMP-9与最终NIHSS评分之间存在密切关系（r=0.486，P=0.002）。在多因素逻辑回归模型中，MMP-9值是与最终NIHSS评分相关的唯一因素（比值比[OR]4.54，95%可信区间[CI]1.5至13.75）。MMP-9为142.18 ng/mL这一切点，在研究结束时评估患者NIHSS评分（<8或≥8）的阳性预测值为94.4%。再通发生时，最终MMP-2和MMP-9水平显著降低（MMP-2：528±144.3对681.4±239.2 ng/mL，P=0.031；MMP-9：110.2±100.9对244.8±130 ng/mL，P=0.004）。平均MMP-9与梗死体积之间存在正相关（r=0.385，P=0.022）。
MMPs参与人类缺血性脑卒中急性期。MMP-9水平与神经功能缺损、大脑中动脉闭塞及梗死体积相关。
