Wang Shiquan, Wei Haidong, Cai Min, Lu Yan, Hou Wugang, Yang Qianzi, Dong Hailong, Xiong Lize
1. Department of Anesthesiology, Xijing Hospital, Forth Military Medical University, Xi'an, China; ; 4. Dr Shiquan Wang and Dr Haidong Wei equally contributed to this work.
2. Department of Anesthesiology, the Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, China; ; 4. Dr Shiquan Wang and Dr Haidong Wei equally contributed to this work.
Int J Biol Sci. 2014 Apr 8;10(4):457-65. doi: 10.7150/ijbs.7562. eCollection 2014.
Stroke has severe consequences in postmenopausal women. As replacement therapy of estrogen have various adverse effects and the undermined outcomes. Genistein, a natural phytoestrogen, has been suggested to be a potential neuroprotective agent for such stroke patients. However, the role of genistein and its underlying mechanism in ovariectomized mice has not yet been evaluated. In the present study, ovariectomized mice were treated with genistein (10 mg/kg) or vehicle daily for two weeks before developing transient cerebral ischemia (middle cerebral artery occlusion). The neurological manifestation was evaluated, and infarct volumes were demonstrated by 2,3,5-triphenyltetrazolium chloride staining at 24 h after reperfusion. In addition, phosphorylation of extracellular signal-regulated kinase (ERK) was detected by Western blotting and immunofluorescence staining, and cellular apoptosis was evaluated in the ischemic penumbra. We found that treatment with genistein reduced infarct volumes, improved neurological outcomes and attenuated cellular apoptosis at 24 h after reperfusion. ERK1/2 showed increased phosphorylation by genistein treatment after reperfusion, and an ERK1/2 inhibitor U0126 abolished this protective effect of genistein in terms of infarct volumes, neurological scores and cellular apoptosis. Our findings indicate that treatment with genistein can reduce the severity of subsequent stroke episodes, and that this beneficial function is associated with ERK activation.
中风对绝经后女性有严重影响。由于雌激素替代疗法有各种不良反应且疗效不佳。金雀异黄素，一种天然植物雌激素，已被认为是此类中风患者潜在的神经保护剂。然而，金雀异黄素在去卵巢小鼠中的作用及其潜在机制尚未得到评估。在本研究中，在短暂性脑缺血（大脑中动脉闭塞）发生前两周，每天用金雀异黄素（10毫克/千克）或赋形剂处理去卵巢小鼠。评估神经学表现，并在再灌注后24小时通过2,3,5-三苯基氯化四氮唑染色显示梗死体积。此外，通过蛋白质印迹法和免疫荧光染色检测细胞外信号调节激酶（ERK）的磷酸化，并在缺血半暗带评估细胞凋亡。我们发现，金雀异黄素治疗可减少再灌注后24小时的梗死体积，改善神经学结果并减轻细胞凋亡。再灌注后，金雀异黄素治疗使ERK1/2的磷酸化增加，而ERK1/2抑制剂U0126在梗死体积、神经学评分和细胞凋亡方面消除了金雀异黄素的这种保护作用。我们的研究结果表明，金雀异黄素治疗可降低随后中风发作的严重程度，且这种有益作用与ERK激活有关。
