Neuroprotective Effects of Genistein in Mongolian Gerbils: Estrogen Receptor-β Involvement
Neuroprotective Effects of Genistein in Mongolian Gerbils: Estrogen Receptor-β Involvement
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DOI：
10.1254/jphs.10164fp
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发表时间：
2010-10-01
影响因子：
3.5
通讯作者：
Sala, Mariaelvina
中科院分区：
文献类型：
--
作者：
Donzelli, Andrea;Braida, Daniela;Sala, Mariaelvina
染料木黄酮是一种天然存在的植物来源的植物雌激素，存在于人类饮食中，已知具有一些有益的效果。本研究通过沙土鼠全脑缺血模型的脑电图和行为相关性研究了染料木黄酮的神经保护作用。在测试的剂量范围内，染料木黄酮（3和10 mg/kg）在再灌注后5 min给药，可拮抗缺血7天后缺血诱导的脑电图总谱功率降低，完全防止缺血1天后缺血诱导的过度运动，逆转由筑巢行为和物体识别试验评价的缺血诱导的记忆障碍，并可降低脑缺血后的脑电活动。在再灌注7天后评估，降低脑中丙二醛的过度产生;并充分促进CA海马子区锥体细胞的存活。雌激素受体β（ER β）的选择性拮抗剂4-[2-苯基-5，7-双（三氟甲基）吡唑并[1，5-α]嘧啶-3-基]苯酚（PHTPP）在颈动脉闭塞前30分钟给予，完全阻止了剂量为3 mg/kg的染料木黄酮的神经保护作用。这些结果证明了染料木黄酮通过激活ER β的神经保护作用，并为植物雌激素作为化合物有益地影响脑损伤而不具有雌激素的缺点的真正潜力的日益增长的兴趣提供了进一步的理由。
Genistein is a naturally occurring plant-derived phytoestrogen, present in the human diet, known to possess some beneficial effects. The present study investigated the effect of genistein on neuroprotection evaluated through electroencephalographic and behavioural correlates in a model of global cerebral ischemia in gerbils. Over the dose range tested, genistein (3 and 10 mg/kg), given 5 min after recirculation antagonized the ischemia-induced electroencephalographic total spectral power decrease 7 days after ischemia; fully prevented ischemia-induced hyperlocomotion evaluated 1 day after ischemia; reversed ischemia-induced memory impairment evaluated through both nest building behaviour and object recognition test; decreased malondialdehyde overproduction in the brain, evaluated 7 days after reperfusion; and fully promoted the survival of pyramidal cells in the CA, hippocampal subfield. The selective antagonist for estrogen receptor-beta (ER beta), 4[2-phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-alpha]pyrimidin-3-yl]phenol (PHTPP) given 30 min before carotid occlusion, fully prevented the neuroprotective effect of genistein at the dose of 3 mg/kg. These results demonstrate the neuroprotective effect of genistein through the activation of ER beta and provide further grounds for the growing interest concerning the true potential of phytoestrogens as compounds to beneficially affect brain injury without having the disadvantages of estrogens.