Department of Human Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Department of Human Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Brain Res Bull. 2019 Mar;146:136-142. doi: 10.1016/j.brainresbull.2018.11.003. Epub 2018 Nov 13.
Matrix metalloproteinases (MMPs) cleave almost all components of the extracellular matrix (ECM) and cause acute neurovascular disruption and parenchymal destruction. Previously, MMPs inhibition was considered to be a therapeutic strategy in early stages of ischemia. This study was designed to investigate whether early MMPs inhibition could promote the recovery of cerebral ischemia. Male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAO) for 1 h and reperfusion. The rats were divided into three groups: sham + vehicle (S + V) group, MCAO + vehicle (M + V) group, and MCAO + GM6001 (M + G) group. Infarct volume was assessed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, and the expression of GFAP, IBA1, p-ERK, ERK, and MMP9 were evaluated by Western blot and immunofluorescence staining on 1, 4, 7, and 14 days after MCAO. Neuronal apoptosis was assessed by Fluoro-Jade C staining. The results showed that MMPs inhibition significantly increased the infarct volume and the expressions of GFAP and IBA1 in the M + V group were much higher than those in the M + G group; whereas the expression of p-ERK was upregulated in both the M + V and M + G groups. These findings suggest that MMPs promote the activation and migration of astrocytes and microglia to form protected zone in the penumbra and lessen the infarct volume after cerebral ischemic stroke.
基质金属蛋白酶（MMPs）几乎可以降解细胞外基质（ECM）的所有成分，并导致急性神经血管功能障碍和实质破坏。此前，MMPs 抑制被认为是缺血早期的一种治疗策略。本研究旨在探讨早期 MMPs 抑制是否能促进脑缺血的恢复。雄性 Sprague-Dawley 大鼠行右侧大脑中动脉闭塞（MCAO）1 小时后再灌注。将大鼠分为三组：假手术+载体（S+V）组、MCAO+载体（M+V）组和 MCAO+GM6001（M+G）组。通过 2,3,5-三苯基氯化四氮唑（TTC）染色评估梗死体积，通过 Western blot 和免疫荧光染色评估 GFAP、IBA1、p-ERK、ERK 和 MMP9 的表达，在 MCAO 后 1、4、7 和 14 天进行评估。通过氟化物-Jade C 染色评估神经元凋亡。结果表明，MMPs 抑制显著增加了梗死体积，M+V 组 GFAP 和 IBA1 的表达明显高于 M+G 组；而 M+V 和 M+G 组的 p-ERK 表达均上调。这些发现表明，MMPs 促进了星形胶质细胞和小胶质细胞的激活和迁移，在半影区形成保护带，减少脑缺血性卒中后的梗死体积。
