Role of Wnt/β-catenin in the tolerance to focal cerebral ischemia induced by electroacupuncture pretreatment
Role of Wnt/β-catenin in the tolerance to focal cerebral ischemia induced by electroacupuncture pretreatment
复制标题
Wnt/β-catenin 在电针预处理诱发局灶性脑缺血耐受中的作用
DOI：
10.1016/j.neuint.2016.03.011
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发表时间：
2016-07-01
影响因子：
4.2
通讯作者：
Wang, Junlu
中科院分区：
文献类型：
--
作者：
He, Xin;Mo, Yunchang;Wang, Junlu
以往的研究表明，电针预处理可迅速提高局灶性脑缺血的耐受性，Wnt/β-catenin在细胞存活和增殖中起重要作用。在本研究中，我们研究了Wnt/β-catenin在电针预处理诱导的神经保护中的作用。电针预处理后2 h，采用大脑中动脉阻塞（MCAO）法制备局灶性脑缺血模型。再灌注后24 h评价神经元存活、细胞凋亡和Garcia神经功能缺损评分。再灌注24小时后，采用Morris水迷宫实验检测大鼠学习记忆功能.最后，在存在和不存在Wnt/β-连环蛋白拮抗剂Dickkopf-1（Dkk-1）的情况下，研究了β-连环蛋白的表达和B细胞淋巴瘤2（Bcl-2）/Bcl-2相关X蛋白（Bax）的比例，该拮抗剂在MCAO前30分钟给药。我们观察到电针预处理显著增加了再灌注后24 h海马神经元β-连环蛋白的表达。此外，电针预处理改善神经功能，减少神经元丢失，抑制细胞凋亡，并逆转再灌注后的学习和记忆障碍。电针的这些有益作用被Dkk-1减弱，Dkk-1有效地逆转了β-连环蛋白的表达。此外，Wnt/β-连环蛋白激动剂的施用上调β-连环蛋白的表达和Bcl-2/Bax比率。这些结果表明，Wnt/β-catenin在EA预处理对脑缺血的保护作用中起作用，从而为EA预处理诱导的局灶性脑缺血快速耐受的新机制提供了证据。(C)2016爱思唯尔有限公司版权所有。
Previous studies have demonstrated that pretreatment with electroacupuncture (EA) elicits rapid tolerance to focal cerebral ischemia and that Wnt/beta-catenin plays an essential role in cell survival and proliferation. In the present study, we investigated the role of Wnt/beta-catenin in EA pretreatment-induced neuroprotection. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 h. Neuronal survival, cell apoptosis, and the Garcia neurological deficit scores were evaluated 24 h after reperfusion. Moreover, learning and memory deficits were assessed 24 hatter reperfusion using the Morris water maze test. Finally, the expression of beta-catenin and the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio were investigated in the presence and absence of the Wnt/beta-catenin antagonist Dickkopf-1 (Dkk-1), which was administered 30 min before MCAO. We observed that EA pretreatment significantly increased the neuronal expression of beta-catenin in the hippocampus 24 h after reperfusion. Moreover, EA pretreatment improved the neurological outcomes, decreased neuronal loss, inhibited apoptosis, and reversed learning and memory deficits following reperfusion. These beneficial effects of EA were attenuated by Dkk-1, which effectively reversed the expression of beta-catenin. Furthermore, the administration of a Wnt/beta-catenin agonist upregulated the expression of beta-catenin and the Bcl-2/Bax ratio. These results suggest that Wnt/beta-catenin plays a role in the protective effects of EA pretreatment against cerebral ischemia, thus providing evidence of a novel mechanism underlying EA-pretreatment-induced rapid tolerance to focal cerebral ischemia. (C) 2016 Elsevier Ltd. All rights reserved.