Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ 85004, USA.
Int J Mol Sci. 2024 Aug 30;25(17):9442. doi: 10.3390/ijms25179442.
Matrix metalloproteinases (MMPs) such as MMP-9, 3, and 2 degrade the cellular matrix and are believed to play a crucial role in ischemic stroke. We examined how the duration of ischemia (up to 4 h) and treatment with recombinant tissue plasminogen activator altered the comparative expression of these MMPs in experimental ischemic stroke with reperfusion. Both prolonged ischemia and r-tPA treatment markedly increased MMP-9 expression in the ischemic hemisphere (all < 0.0001). The duration of ischemia and r-tPA treatment also significantly increased MMP-2 expression ( < 0.01-0.001) in the ischemic hemisphere ( < 0.01) but to a lesser degree than MMP-9. In contrast, MMP-3 expression significantly decreased in the ischemic hemisphere ( < 0.001) with increasing duration of ischemia and r-tPA treatment ( < 0.05-0001). MMP-9 expression was prominent in the vascular compartment and leukocytes. MMP-2 expression was evident in the vascular compartment and MMP-3 in NeuN+ neurons. Prolonging the duration of ischemia (up to 4 h) before reperfusion increased brain hemorrhage, infarction, swelling, and neurologic disability in both saline-treated (control) and r-tPA-treated mice. MMP-9 and MMP-2 expression were significantly positively correlated with, and MMP-3 was significantly negatively correlated with, infarct volume, swelling, and brain hemorrhage. We conclude that in experimental ischemic stroke with reperfusion, the duration of ischemia and r-tPA treatment significantly altered MMP-9, 3, and 2 expression, ischemic brain injury, and neurological disability. Each MMP showed unique patterns of expression that are strongly correlated with the severity of brain infarction, swelling, and hemorrhage. In summary, in experimental ischemic stroke in male mice with reperfusion, the duration of ischemia, and r-tPA treatment significantly altered the immunofluorescent expression of MMP-9, 3, and 2, ischemic brain injury, and neurological disability. In this model, each MMP showed unique patterns of expression that were strongly correlated with the severity of brain infarction, swelling, and hemorrhage.
基质金属蛋白酶（MMPs），如 MMP-9、3 和 2，可降解细胞基质，被认为在缺血性卒中中发挥关键作用。我们研究了缺血持续时间（长达 4 小时）和重组组织型纤溶酶原激活剂（r-tPA）治疗如何改变实验性缺血再灌注后这些 MMP 的比较表达。延长缺血和 r-tPA 治疗均显著增加缺血半球的 MMP-9 表达（均 < 0.0001）。缺血持续时间和 r-tPA 治疗也显著增加缺血半球的 MMP-2 表达（< 0.01-0.001）（< 0.01），但程度低于 MMP-9。相比之下，随着缺血持续时间和 r-tPA 治疗的增加，MMP-3 在缺血半球的表达显著降低（< 0.001）（< 0.05-0001）。MMP-9 表达主要在血管腔和白细胞中明显。MMP-2 表达在血管腔中明显，MMP-3 在 NeuN+神经元中明显。在再灌注前延长缺血持续时间（长达 4 小时）会增加盐水治疗（对照）和 r-tPA 治疗的小鼠的脑出血、梗死、肿胀和神经功能障碍。MMP-9 和 MMP-2 表达与梗死体积、肿胀和脑出血呈显著正相关，而 MMP-3 与梗死体积、肿胀和脑出血呈显著负相关。我们得出结论，在实验性缺血再灌注后卒中中，缺血持续时间和 r-tPA 治疗显著改变了 MMP-9、3 和 2 的表达、缺血性脑损伤和神经功能障碍。每种 MMP 的表达模式都不同，与脑梗死、肿胀和出血的严重程度密切相关。总之，在雄性小鼠的实验性缺血再灌注卒中中，缺血持续时间和 r-tPA 治疗显著改变了 MMP-9、3 和 2 的免疫荧光表达、缺血性脑损伤和神经功能障碍。在该模型中，每种 MMP 的表达模式都不同，与脑梗死、肿胀和出血的严重程度密切相关。
