Matrix metalloproteinases increase very early during experimental focal cerebral ischemia
Matrix metalloproteinases increase very early during experimental focal cerebral ischemia
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DOI：
10.1097/00004647-199906000-00005
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发表时间：
1999-06-01
影响因子：
6.3
通讯作者：
del Zoppo, GJ
中科院分区：
文献类型：
--
作者：
Heo, JH;Lucero, J;del Zoppo, GJ
局灶性脑缺血时微血管的完整性丧失。基底层和细胞外基质的降解是导致血管完整性丧失的部分原因。基质金属蛋白酶（MMP）可能在基底膜降解中起主要玛丽。采用明胶酶谱法，对27只非人灵长类动物大脑中动脉闭塞/再灌注（MCAO/R）后不同时间缺血和非缺血基底节10 μ m冰冻切片及血浆中MMP-2和MMP-9的活性进行了研究。明胶分解活性与相邻切片缺血区平行细胞dUTP掺入进行比较。在脑中，MMP-2的积分密度在MCAO后1小时显著增加，此后持续升高。基质金属蛋白酶2的表达与神经元损伤程度及损伤神经元数目呈高度相关（r = 0.9763，SE = 0.004，2 P < 0.0008）。基质金属蛋白酶-9的表达仅在出血性转化的受试者中显著增加。在血浆中，只有MMP-9在MCAO 2小时短暂增加。这些发现突出了MMP-2在基底层降解导致神经元损伤中的早期潜在作用，以及MMP-9与局灶性脑缺血后出血性转化的关联。
Microvascular integrity is lost during focal cerebral ischemia. The degradation of the basal lamina and extracellular matrix are, in part, responsible for the loss of vascular integrity. Matrix metalloproteinases (MMPs) may play a pri mary role in basal lamina degradation. By using a sensitive modification of gelatin zymography, the authors investigated the activity of MMP-2 and MMP-9 in frozen 10-mu m sections of ischemic and nonischemic basal ganglia and plasma samples of 27 non-human primates after middle cerebral artery occlusion/ reperfusion (MCAO/R) for various periods. The gelatinolytic activities were compared with parallel cell dUTP incorporation in the ischemic zones of adjacent sections. In the brain, the integrated density of MMP-2 increased significantly by 1 hour after MCAO and was persistently elevated thereafter. Matrix metalloproteinase-2 expression was highly correlated with the extent of neuron injury and the number of injured neurons (r = 0.9763, SE = 0.004,2P < 0.0008). Matrix metalloproteinase-9 expression only was significantly increased in subjects with hemorrhagic transformation. In plasma, only MMP-9 increased transiently at 2 hours of MCAO. These findings highlight the early potential role of MMP-2 in the degradation of basal lamina leading to neuronal injury, and an association of MMP-9 with hemorrhagic transformation after focal cerebral ischemia.