Neuroprotective efficacy and therapeutic window of Forsythoside B: In a rat model of cerebral ischemia and reperfusion injury
Neuroprotective efficacy and therapeutic window of Forsythoside B: In a rat model of cerebral ischemia and reperfusion injury
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DOI：
10.1016/j.ejphar.2010.04.055
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发表时间：
2010-08-25
影响因子：
5
通讯作者：
Hou, Jian
中科院分区：
文献类型：
--
作者：
Jiang, Wang-Lin;Tian, Jing-Wei;Hou, Jian
本研究旨在探讨连翘酯苷B的神经保护作用及其机制。将雄性Sprague-Dawley大鼠进行大脑中动脉闭塞1 h，然后再灌注23 h。再灌注后15 min，大鼠静脉注射连翘酯苷B。结果表明，连翘酯苷B在8 mg/kg以上对脑缺血再灌注大鼠有明显的神经保护作用。连翘酯苷B（20 mg/kg）在脑缺血和再灌注后1 h、3 h和5 h延迟给药后仍表现出显著的神经保护活性。连翘酯苷B 20 mg/kg可减轻脑梗死面积和脑水肿，降低脑伊文思蓝外渗和髓过氧化物酶（MPO）活性，抑制脑磷酸化I κ B-α和核转录因子κ B（NF-κ B）表达。同时，免疫组织化学染色显示NF-κ B表达减少，而循环多形核白细胞增加。提示连翘酯苷B具有较好的神经保护作用，其作用时间窗较好，能减轻脑缺血再灌注损伤程度，减轻血脑屏障（blood-brain barrier，BB B）的破坏，其保护作用可能与抑制炎症反应有关。(C)2010爱思唯尔有限公司版权所有。
The present study was to investigate the neuroprotective efficacy and mechanism of Forsythoside B. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 1 h followed by reperfusion for 23 h. Rats received an intravenous bolus injection of Forsythoside B at 15 min after reperfusion. The results showed that Forsythoside B at doses higher than 8 mg/kg produced a significant neuroprotective potential in cerebral ischemia and reperfusion rats. Forsythoside B (20 mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 1 h, 3 h and 5 h after cerebral ischemia and reperfusion. Forsythoside B 20 mg/kg attenuated histopathological damage as demonstrated by smaller brain infarct size and brain edema, decreased cerebral Evans blue extravasation and myeloperoxidase (MPO) activity, inhibited cerebral phosphor-I kappa B-alpha and nuclear transcription factors kappaB (NF-kappa B) expression. Meanwhile, NF-kappa B expression with immunohistochemical staining was reduced, while circulating polymorphonuclear leukocytes was increased. All of these findings suggested that Forsythoside B exerted potent neuroprotective effects with a favorable therapeutic time-window, reduce of cerebral ischemia and reperfusion injury degree, attenuating blood-brain barrier (BBB) breakdown, and its protective effects may be due to inhibition of inflammatory response. (C) 2010 Elsevier B.V. All rights reserved.