Horstmann Solveig, Kalb Pamela, Koziol James, Gardner Humphrey, Wagner Simone
Department of Neurology, Medical School, University of Heidelberg, Germany.
Stroke. 2003 Sep;34(9):2165-70. doi: 10.1161/01.STR.0000088062.86084.F2. Epub 2003 Aug 7.
The goal of this study was to determine the temporal profile of several matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), and laminin (an MMP substrate) in human stroke under different treatment paradigms, including thrombolysis and hypothermia.
We serially measured the serum levels of MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, and laminin in 50 patients with acute ischemic stroke using zymography or enzyme-linked immunosorbent assay. Patients were treated with heparin, therapeutic thrombolysis, or hypothermia. Scandinavian Stroke Scale scores were obtained at baseline. Infarct volume was measured with CT scanning on day 4 after stroke onset. Healthy persons were used as control subjects.
MMP-2 and MMP-9 increased during the course of ischemia, whereas intact laminin and TIMP-2 decreased significantly (P<0.05). MMP-9 and laminin levels varied significantly by infarct size (P=0.001) and therapy (P=0.0005). MMP-9 levels were significantly higher in patients treated with tissue plasminogen activator (tPA) compared with patients treated with hypothermia. The cleaved form of MMP-9 was found solely in 4 patients treated with tPA. Intact laminin levels were significantly lower in the tPA group than in the hypothermia group.
Selected MMPs and TIMPs are involved in the pathophysiology of acute stroke. This is also reflected by changes in laminin. Treatment paradigms differentially influence levels of MMP-9 and laminin. Combination therapies explicitly involving MMP inhibition could be of value in future treatment strategies.
本研究的目的是确定在不同治疗模式下，包括溶栓和低温治疗，人类中风中几种基质金属蛋白酶（MMPs）、MMP组织抑制剂（TIMPs）和层粘连蛋白（一种MMP底物）的时间变化情况。
我们使用酶谱法或酶联免疫吸附测定法，连续测量了50例急性缺血性中风患者血清中MMP - 2、MMP - 3、MMP - 9、MMP - 13、TIMP - 1、TIMP - 2和层粘连蛋白的水平。患者接受肝素、治疗性溶栓或低温治疗。在基线时获得斯堪的纳维亚卒中量表评分。在中风发作后第4天用CT扫描测量梗死体积。健康人作为对照。
在缺血过程中，MMP - 2和MMP - 9升高，而完整的层粘连蛋白和TIMP - 2显著降低（P<0.05）。MMP - 9和层粘连蛋白水平因梗死大小（P = 0.001）和治疗方法（P = 0.0005）而有显著差异。与接受低温治疗的患者相比，接受组织纤溶酶原激活剂（tPA）治疗的患者MMP - 9水平显著更高。仅在4例接受tPA治疗的患者中发现了MMP - 9的裂解形式。tPA组中完整层粘连蛋白水平显著低于低温治疗组。
特定的MMPs和TIMPs参与急性中风的病理生理过程。这也反映在层粘连蛋白的变化中。治疗模式对MMP - 9和层粘连蛋白水平有不同影响。明确涉及MMP抑制的联合治疗可能在未来治疗策略中有价值。
