Early activation of matrix metalloproteinase-9 is associated with blood-brain barrier disruption after photothrombotic cerebral ischemia in rats
Early activation of matrix metalloproteinase-9 is associated with blood-brain barrier disruption after photothrombotic cerebral ischemia in rats
复制标题
DOI：
10.1007/s00701-009-0431-1
复制
发表时间：
2009-12-01
影响因子：
2.4
通讯作者：
Kim, Hyung-Seok
中科院分区：
文献类型：
--
作者：
Piao, Min-Sheng;Lee, Jung-Kil;Kim, Hyung-Seok
基质金属蛋白酶（MMP）的激活是脑缺血期间血脑屏障（BBB）破坏的关键事件。据报道，在 MMP 中，MMP-2 和 MMP-9 的表达在缺血发生后显着升高。本研究的目的是探讨哪一种对光血栓性脑缺血中的血脑屏障破坏更为重要。体重250-300g的雄性Sprague-Dawley大鼠通过光血栓形成局灶性脑缺血。通过明胶酶谱法在 2 小时至 7 天的不同时间评估 MMP-2 和 MMP-9 活性。采用伊文思蓝染料分光光度法评估血脑屏障完整性。脑缺血后2小时内伊文思蓝外渗增加，损伤后12和24小时达到最大，然后逐渐减少。早在局灶性缺血事件后 2 小时即可检测到 MMP-9 蛋白活性；它在缺血后6小时迅速增加，并在缺血事件后48小时达到最高水平。此后，MMP-9 水平突然下降，并在损伤后 72 小时恢复到基线。相比之下，MMP-2蛋白活性在局灶性缺血损伤后6小时上调，并在事件后72小时达到最高水平。损伤后MMP-2水平持续升高7天。MMP-9的早期激活与BBB通透性增加相关。我们的研究结果表明，MMP-9 是大鼠光血栓性脑缺血后 BBB 破坏和随后脑损伤的关键因素。
The activation of matrix metalloproteinases (MMPs) is a critical event for disruption of the blood-brain barrier (BBB) during cerebral ischemia. Among the MMPs, MMP-2, and MMP-9 expression were reported to be significantly elevated after the onset of ischemia. The aim of this study was to investigate which one is more significant for BBB disruption in the photothrombotic cerebral ischemia.Male Sprague-Dawley rats weighing 250-300 g received focal cerebral ischemia by photothrombosis. MMP-2 and MMP-9 activities were assessed by gelatin zymography at various times from 2 h to 7 days. The BBB integrity was assessed using Evans blue dye with a spectrophotometric assay.The Evans blue extravasation was increased within 2 h after cerebral ischemia, and was maximal at 12 and 24 h after the injury, and then gradually decreased. MMP-9 protein activity was detected as early as 2 h after the focal ischemic event; it rapidly increased at 6 h after ischemia, and reached a maximum level 48 h after the ischemic event. Thereafter, the MMP-9 level abruptly decreased and returned to the baseline at 72 h after the insult. By contrast, the MMP-2 protein activity was up-regulated at 6 h after the focal ischemic insult, and reached a maximum level at 72 h after the event. The elevated MMP-2 levels persisted for 7 days after the injury.The early activation of MMP-9 was correlated with the increase in the permeability of the BBB. Our findings suggest that MMP-9 is the key factor involved in BBB disruption and subsequent brain injury after photothrombotic cerebral ischemia in rats.