Promoting neurogenesis via Wnt/β-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury
Promoting neurogenesis via Wnt/β-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury
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通过Wnt/β-catenin信号通路促进神经发生解释了莫诺苷对脑缺血损伤的神经恢复作用
DOI：
10.1016/j.ejphar.2014.05.019
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发表时间：
2014-09-05
影响因子：
5
通讯作者：
Ji, Xun-Ming
中科院分区：
文献类型：
--
作者：
Sun, Fang-Ling;Wang, Wen;Ji, Xun-Ming
缺血性卒中是全世界成年人死亡和永久性残疾的主要原因。成年哺乳动物脑缺血引发的神经发生可能为中风治疗提供见解。莫诺苷是C.具有神经保护作用的药用植物。本研究的目的是在大鼠局灶性脑缺血模型中检测莫诺苷是否通过Wnt/β-catenin信号通路促进神经发生以促进脑恢复。在缺血后7天，每天一次灌胃给予浓度为30、90和270 mg/kg的莫诺苷。Ludmila Belayev评分测试检测神经功能。用Ki-67和Nestin免疫荧光染色观察内源性神经干细胞在室管膜下区（SVZ）的神经发生。Western blotting检测Wnt/beta-catenin信号通路相关蛋白的表达。莫诺苷显著促进缺血后7天脑恢复的神经发生。Writ 3a、β-catenin和Tcf-4的表达增加，同时沿着下游转录因子Pax 6和神经生成素2（Ngn 2）的激活，提示莫诺苷的神经修复作用可能与Wnt/β-catenin信号通路有关。这些数据为了解莫诺苷神经修复作用的机制提供了支持，并为缺血性卒中的治疗提供了潜在的新策略。(C)2014爱思唯尔有限公司版权所有。
Ischemic stroke is a leading cause of mortality and permanent disability in adults worldwide. Neurogenesis triggered by ischemia in the adult mammalian brain may provide insights into stroke treatment. Morroniside is an active component of sarcocarp of C. officinalis that have shown neuroprotective effects. The aim of the present study is to test whether morroniside promotes neurogenesis via Wnt/beta-catenin signaling pathway for brain recovery in a rat model of focal cerebral ischemia. Morroniside was administered intragastrically once daily at the concentrations of 30, 90 and 270 mg/kg for 7 days post-ischemia. Neurological functions were detected by Ludmila Belayev score tests. Endogenous neural stem cells responses were investigated with immunofluorescence staining of Ki-67 and Nestin to identify the neurogenesis in the subventricular zone (SVZ). The expression of proteins involved in and related to Wnt/beta-catenin signaling pathway was detected by western blotting analysis. Morroniside significantly promoted neurogenesis for brain recovery 7 days post-ischemia. Increased expression of Writ 3a, P-catenin and T-cell transcription factor-4 (Tcf-4), along with activation of downstream transcription factors Pax6 and neurogenin2 (Ngn2), indicated that the neurorestorative effects of morroniside may be associated with Wnt/beta-catenin signaling pathway. These data provide support for understanding the mechanisms of morroniside in neurorestorative effects and suggest a potential new strategy for ischemic stroke treatment. (C) 2014 Elsevier B.V. All rights reserved.