Quercetin ameliorates ischemia/reperfusion-induced cognitive deficits by inhibiting ASK1/JNK3/caspase-3 by enhancing the Akt signaling pathway
Quercetin ameliorates ischemia/reperfusion-induced cognitive deficits by inhibiting ASK1/JNK3/caspase-3 by enhancing the Akt signaling pathway
复制标题
槲皮素通过增强 Akt 信号通路抑制 ASK1/JNK3/caspase-3，从而改善缺血/再灌注引起的认知缺陷。
DOI：
10.1016/j.bbrc.2016.07.068
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发表时间：
2016-09-09
影响因子：
3.1
通讯作者：
Zhang, Fayong
中科院分区：
文献类型：
--
作者：
Pei, Bing;Yang, Miaomiao;Zhang, Fayong
脑缺血/再灌注（I/R）是全世界严重残疾和死亡的主要原因。然而，减少脑I/R损伤的有害影响的治疗选择是有限的。最近的研究表明，槲皮素介导的神经保护作用与激活Akt信号通路在脑I/R脑。因此，本研究的目的是进一步探讨脑I/R损伤所致认知功能障碍的机制以及槲皮素对这些机制的影响。首先，我们分别采用旷场试验和Morris水迷宫试验评估焦虑样行为和认知障碍。接下来，我们通过甲酚紫法对海马神经元进行染色来检查凋亡的严重程度。第三，采用Western blot检测缺血再灌注损伤后总Akt、磷酸化Akt、ASK 1、JNK 3、c-Jun和caspase-3的表达。我们的研究结果显示，双侧颈总动脉闭塞小鼠表现出严重的焦虑样行为，学习记忆障碍，细胞损伤和凋亡。这些严重的影响减弱了槲皮素的管理。Western blot结果显示，槲皮素可增加脑I/R损伤后p-Akt的表达，降低p-ASK 1、p-JNK 3和caspase-3的表达，抑制神经元凋亡。相反，用LY 294002（Akt 1的选择性抑制剂）处理逆转了槲皮素的作用。总之，这些研究结果强调了槲皮素通过Akt信号通路在保护认知缺陷和抑制神经元凋亡方面的重要作用。我们相信，槲皮素可能被证明是一个有用的治疗成分在治疗脑I/R疾病在不久的将来。(C)2016 Elsevier Inc. All rights reserved.
Cerebral ischemia/reperfusion (I/R) is a major cause of severe disability and death all worldwide. However, therapeutic options to minimize the detrimental effects of cerebral I/R injury are limited. Recent research has demonstrated that quercetin mediates neuroprotective effects associated with the activation of the Akt signaling pathway in the cerebral I/R brain. Therefore, the aim of this study was to further investigate the mechanisms of cognitive deficits induced by cerebral I/R injury and the effects of quercetin on these mechanisms. First, we assessed anxiety-like behavioral and cognitive impairment using the open field test and the Morris water maze test, respectively. Next, we examined the severity of apoptosis by staining hippocampal neurons by the Cresyl violet method. Third, we used western blot analysis to investigate the expression of total and phosphorylated Akt, ASK1, JNK3, c-Jun and caspase-3 after I/R injury. Our results revealed that mice subjected to bilateral common carotid occlusion exhibited severe anxiety-like behavior, learning and memory impairment, cell damage and apoptosis. These severe effects were attenuated by administration of quercetin. Further, western blot analysis revealed that quercetin increased p-Akt expression and decreased p-ASK1, p-JNK3 and cleaved caspase-3 expression after cerebral I/R injury and led to inhibition of neuronal apoptosis. Conversely, treatment with LY294002 (a selective inhibitor of Akt1) reversed the effects of quercetin. In conclusion, these findings highlight the important role of quercetin in protecting against cognitive deficits and inhibiting neuronal apoptosis via the Akt signaling pathway. We believe that quercetin might prove to be a useful therapeutic component in treating cerebral I/R diseases in the near future. (C) 2016 Elsevier Inc. All rights reserved.