Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, China.
CNS Neurosci Ther. 2012 Oct;18(10):855-63. doi: 10.1111/j.1755-5949.2012.00366.x. Epub 2012 Aug 23.
Ischemic postconditioning (IPostC) has been proved to have neuroprotective effects for cerebral ischemia, but the underlying mechanism remains elusive. This study aimed at validating the neuroprotective effects of IPostC and investigating whether the neuroprotection of IPostC is associated with matrix metalloproteinase 9 (MMP9) and the extracellular matrix proteins, laminin and fibronectin, following cerebral ischemia/reperfusion in rats.
The rats in middle cerebral artery occlusion (MCAO) group underwent MCAO and reperfusion, and the animals in MCAO + IPostC group were treated by occluding bilateral common carotid arteries for 10 seconds and then reperfusing for 10 seconds for five episodes at the beginning of MCAO. Apoptosis was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of MMP9, laminin, and fibronectin was measured with immunofluorescence and enzyme-linked immunosorbent assay.
IPostC reduced brain edema and infarct volume and improved the neurological function. Furthermore, IPostC decreased cell apoptosis compared with the MCAO group. Compared to the MCAO group, IPostC treatment reduced MMP9 expression. Moreover, the results showed that the expression of laminin and fibronectin significantly increased in the MCAO + IPostC group compared to the MCAO group.
These findings indicated that diminishment of MMP9 expression and the attenuation of degradation of laminin and fibronectin may be involved in the protective mechanisms of postconditioning against cerebral ischemia/reperfusion injury.
缺血后处理（IPostC）已被证明对脑缺血具有神经保护作用，但潜在机制仍不清楚。本研究旨在验证 IPostC 的神经保护作用，并探讨 IPostC 的神经保护作用是否与脑缺血/再灌注后大鼠基质金属蛋白酶 9（MMP9）和细胞外基质蛋白层粘连蛋白和纤维连接蛋白有关。
大脑中动脉闭塞（MCAO）组大鼠行 MCAO 及再灌注，MCAO+IPostC 组动物在 MCAO 开始时行双侧颈总动脉闭塞 10 秒，再灌注 10 秒，共 5 个循环。末端脱氧核苷酸转移酶 dUTP 缺口末端标记染色检测细胞凋亡。免疫荧光和酶联免疫吸附试验检测 MMP9、层粘连蛋白和纤维连接蛋白的表达。
IPostC 减轻脑水肿和梗死体积，改善神经功能。此外，与 MCAO 组相比，IPostC 减少了细胞凋亡。与 MCAO 组相比，IPostC 治疗降低了 MMP9 的表达。此外，结果显示，与 MCAO 组相比，MCAO+IPostC 组的层粘连蛋白和纤维连接蛋白表达显著增加。
这些发现表明，MMP9 表达的减少和层粘连蛋白和纤维连接蛋白降解的减弱可能参与了后处理对脑缺血/再灌注损伤的保护机制。
