Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia
Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia
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DOI：
10.1016/j.neulet.2006.06.010
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发表时间：
2006-09-01
影响因子：
2.5
通讯作者：
Lee, Seong-Ryong
中科院分区：
文献类型：
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作者：
Cho, Jae-Yong;Kim, In-Soo;Lee, Seong-Ryong
槲皮素是一种生物活性物质，对缺血再灌注引起的包括神经组织在内的多种组织的损伤具有抑制作用。槲皮素还被报道对基质金属蛋白酶（MMP）具有抑制作用。由于MMPs在脑缺血损伤的病理生理学中起主要作用，因此槲皮素对脑缺血的保护作用的可能机制仍有待阐明。在本研究中，C57 BL/6小鼠进行20分钟短暂性全脑缺血。激光多普勒血流仪监测脑血流。缺血后72 h处死动物。在缺血前30分钟和缺血后立即向小鼠腹膜内给予槲皮素（50 mg/kg，溶于盐水），然后从第二天起每天给予槲皮素一次，直至处死。本研究旨在观察槲皮素对短暂性脑缺血后神经元损伤的影响。脑缺血后，CA 1、CA 2区内侧部神经元明显受损。在槲皮素处理的小鼠中，迟发性神经元损伤与溶剂处理的小鼠相比显著降低。用槲皮素处理的小鼠显示减弱的脑MMP-9活性。明胶凝胶酶谱显示缺血后MMP-9蛋白的诱导。槲皮素显著抑制缺血诱导的MMP-9升高。原位酶谱显示脑缺血后明胶酶活性升高。槲皮素还抑制CA 1和CA 2区的TdT介导的dUTP缺口末端标记（TUNEL）染色。这些结果表明，槲皮素，一种天然黄酮类化合物，通过抑制MMP-9活性减少全脑缺血诱导的神经元损伤。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Previous studies have demonstrated that quercetin, a bioflavonoid shows the inhibitory effect against ischemia and reperfusion-induced injury in various tissues including neural tissue. Quercetin is also reported to have an inhibitory effect against matrix metalloproteinases (MMPs). Because MMPs are known to play a main role in the pathophysiology of brain ischemic insult, their mechanisms of possible protective effect of quercetin against brain ischemia remain to be clarified. In the present study, C57BL/6 mice were subjected to 20 min transient global brain ischemia. Cerebral blood flow was monitored by laser doppler flowmeter. Animals were sacrificed 72 h after ischemia. Quercetin (50 mg/kg, dissolved in saline) was intraperitoneally administered to mice at 30 min before and immediately after ischemia and from the second day, quercetin was then administered once daily until sacrifice. The present study was undertaken to test the effect of quercetin on neuronal damage after transient cerebral ischemia. Neuronal damages were remarkable in the medial portion of CA1 and CA2 areas after ischemic insult. In quercetin-treated mice, delayed neuronal damage was significantly decreased compared with vehicle-treated mice. Mice treated with quercetin showed attenuated brain MMP-9 activity. Gelatin gel zymography showed an induction of MMP-9 protein after ischemia. Quercetin significantly inhibited ischemia-induced elevation of MMP-9. In situ zymography showed elevations in gelatinase activities after brain ischemia. Quercetin also inhibited TdT-mediated dUTP nick end labeling (TUNEL) staining in CA1 and CA2 areas. These results demonstrate that quercetin, a natural flavonoid reduces global ischemia-induced neuronal damage through inhibition of MMP-9 activity. (c) 2006 Elsevier Ireland Ltd. All rights reserved.