Ning M, Furie K L, Koroshetz W J, Lee H, Barron M, Lederer M, Wang X, Zhu M, Sorensen A G, Lo E H, Kelly P J
Stroke Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Neurology. 2006 May 23;66(10):1550-5. doi: 10.1212/01.wnl.0000216133.98416.b4.
Matrix metalloproteinase-9 (MMP9) is expressed in acute ischemic stroke and up-regulated by tissue plasminogen activator (tPA) in animal models. The authors investigated plasma MMP9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase (TIMP1), in tPA-treated and -untreated stroke patients.
Nonstroke control subjects and consecutive ischemic stroke patients presenting within 8 hours of onset were enrolled. Blood was sampled within 8 hours and at 24 hours, 2 to 5 days and 4 to 6 weeks. MMP9 and TIMP1 were analyzed by ELISA and gel zymography.
Fifty-two cases (26 tPA treated, 26 tPA untreated) and 27 nonstroke control subjects were enrolled. Hyperacute MMP9 was elevated in tPA-treated vs tPA-untreated patients (medians 43 vs 28 ng/mL; p = 0.01). tPA therapy independently predicted hyperacute MMP9 after adjustment for stroke severity, volume, and hemorrhagic transformation (p = 0.01). There was a trend toward lower hyperacute TIMP1 levels in tPA-treated vs tPA-untreated patients (p = 0.06). Hyperacute MMP9 was correlated to poor 3-month modified Rankin Scale outcome (r = 0.58, p = 0.0005).
Tissue plasminogen activator independently predicted plasma matrix metalloproteinase-9 (MMP9) in the first 8 hours after human ischemic stroke. As MMP9 may be an important mediator of hemorrhagic transformation, alternative thrombolytic agents or therapeutic MMP9 inhibition may increase the safety profile of acute stroke thrombolysis.
基质金属蛋白酶-9（MMP9）在急性缺血性卒中时表达，并在动物模型中被组织型纤溶酶原激活剂（tPA）上调。作者研究了tPA治疗和未治疗的卒中患者血浆中的MMP9及其内源性抑制剂金属蛋白酶组织抑制剂（TIMP1）。
纳入非卒中对照受试者和发病8小时内连续就诊的缺血性卒中患者。在8小时内、24小时、2至5天以及4至6周时采集血液样本。通过酶联免疫吸附测定法（ELISA）和凝胶酶谱法分析MMP9和TIMP1。
共纳入52例患者（26例接受tPA治疗，26例未接受tPA治疗）和27名非卒中对照受试者。与未接受tPA治疗的患者相比，接受tPA治疗的患者超急性期MMP9水平升高（中位数分别为43 ng/mL和28 ng/mL；p = 0.01）。在调整卒中严重程度、体积和出血性转化后，tPA治疗独立预测超急性期MMP9水平（p = 0.01）。与未接受tPA治疗的患者相比，接受tPA治疗的患者超急性期TIMP1水平有降低趋势（p = 0.06）。超急性期MMP9与3个月改良Rankin量表预后不良相关（r = 0.58，p = 0.0005）。
组织型纤溶酶原激活剂独立预测人类缺血性卒中后最初8小时内的血浆基质金属蛋白酶-9（MMP9）水平。由于MMP9可能是出血性转化的重要介质，替代溶栓药物或治疗性抑制MMP9可能会提高急性卒中溶栓的安全性。
