Wang Yong, Dong Xianhong, Li Zhengzhao, Wang Wenbo, Tian Jing, Chen Jian
Department of Physiology, Guilin Medical University, Guilin 541004, China.
Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China.
J Neurol Sci. 2014 Apr 15;339(1-2):144-8. doi: 10.1016/j.jns.2014.02.002. Epub 2014 Feb 11.
Isoflavone calycosin is a typical phytoestrogen extracted from Chinese medical herb Radix Astragali. It has been reported that estrogens could provide neuroprotective effects, and dietary intake of phytoestrogens could reduce stroke injury in cerebral ischemia/reperfusion (I/R) animal models. In the present study, we investigate the molecular mechanisms underlying the neuroprotective effects of calycosin on middle cerebral artery occlusion (MCAO) rats. Focal cerebral ischemia was induced in male rats by MCAO, neurological deficits and brain edema was evaluated after 24h of reperfusion. The results shown calycosin significantly reduced the infarcted volume and the brain water content, and improved the neurological deficit. To provide insight into the functions of estrogen receptor (ER)-mediated signaling pathway in neuroprotection by calycosin, the expression of miR-375, ER-α, RASD1 (Dexamethasone-induced Ras-related protein 1) and Bcl-2 was determined by RT-PCR or western blot assay. Calycosin exhibited a downregulation of RASD1, and an upregulation of ER-α, miR-375 and Bcl-2. Our finding illustrated that calycosin had been shown neuroprotective effects in cerebral ischemia/reperfusion rats, and the molecular mechanisms may correlate with the positive feedback between ER-α and miR-375, along with the regulation of downstream targets.
异黄酮毛蕊异黄酮是从中药黄芪中提取的一种典型的植物雌激素。据报道，雌激素可提供神经保护作用，而饮食中摄入植物雌激素可减轻脑缺血/再灌注（I/R）动物模型中的中风损伤。在本研究中，我们探讨了毛蕊异黄酮对大脑中动脉闭塞（MCAO）大鼠神经保护作用的分子机制。通过MCAO诱导雄性大鼠局灶性脑缺血，再灌注24小时后评估神经功能缺损和脑水肿情况。结果显示，毛蕊异黄酮显著减少了梗死体积和脑含水量，并改善了神经功能缺损。为了深入了解雌激素受体（ER）介导的信号通路在毛蕊异黄酮神经保护中的作用，通过RT-PCR或蛋白质印迹分析测定了miR-375、ER-α、RASD1（地塞米松诱导的Ras相关蛋白1）和Bcl-2的表达。毛蕊异黄酮表现出RASD1的下调以及ER-α、miR-375和Bcl-2的上调。我们的研究结果表明，毛蕊异黄酮在脑缺血/再灌注大鼠中具有神经保护作用，其分子机制可能与ER-α和miR-375之间的正反馈以及下游靶点的调节有关。
