RESVERATROL PROTECTS AGAINST SPINAL CORD INJURY BY ACTIVATING AUTOPHAGY AND INHIBITING APOPTOSIS MEDIATED BY THE SIRT1/AMPK SIGNALING PATHWAY
RESVERATROL PROTECTS AGAINST SPINAL CORD INJURY BY ACTIVATING AUTOPHAGY AND INHIBITING APOPTOSIS MEDIATED BY THE SIRT1/AMPK SIGNALING PATHWAY
复制标题
白藜芦醇通过激活自噬并抑制 Sirt1/ampk 信号通路介导的细胞凋亡来预防脊髓损伤
DOI：
10.1016/j.neuroscience.2017.02.027
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发表时间：
2017-04-21
期刊：
影响因子：
3.3
通讯作者：
Mei, Xifan
中科院分区：
文献类型：
--
作者：
Zhao, Haosen;Chen, Shurui;Mei, Xifan
脊髓损伤（SCI）是一种几乎没有有效治疗的破坏性疾病。白藜芦醇是一种多酚类化合物，在许多神经退行性疾病中表现出神经保护作用。然而，白藜芦醇对脊髓损伤的确切作用及机制尚不清楚。腺苷5'-磷酸活化蛋白激酶（AMPK）及其下游蛋白质Sirtuin 1（SIRT 1）在能量代谢、抵抗抗性、维持细胞内蛋白质稳态等方面起着重要作用。本研究旨在探讨白藜芦醇对脊髓损伤的作用及其与SIRT 1/AMPK信号通路、自噬和凋亡的关系。为了确定白藜芦醇对SCI恢复的作用，采用脊髓挫伤模型。大鼠在挫伤后立即接受白藜芦醇或DMSO治疗。我们确定，Basso，Beattie和Bresnahan（BBB）评分显着较高的损伤大鼠用白藜芦醇治疗。尼氏染色和HE染色显示，白藜芦醇治疗显着减少运动神经元的损失和损伤的大小在脊髓损伤大鼠相比，溶剂处理的动物。损伤后7天，通过Western blot、逆转录-聚合酶链反应（RT-PCR）和免疫组织化学分析评估脊髓组织中SIRT 1/AMPK信号通路、自噬和凋亡蛋白表达的变化。白藜芦醇处理的动物中SIRT 1、p-AMPK、Beclin-1、LC 3-B和Bcl-2的表达升高，而p62、切割型Caspase-3、Caspase-9和Bcl-2相关X蛋白（Bax）的表达受到抑制。用白藜芦醇单独或与化合物C（AMPK抑制剂）或EX 527（SIRT 1抑制剂）组合处理的原代神经元的免疫荧光分析揭示，用抑制剂处理阻断细胞中增加的LC 3-B表达并增加TUNEL阳性细胞的部分。综上所述，这些结果表明，白藜芦醇通过调节SIRT 1-AMPK信号通路介导的自噬和凋亡对SCI发挥神经保护作用。(C)2017年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Spinal cord injury (SCI) is a devastating condition with few effective treatments. Resveratrol, a polyphenolic compound, has exhibited neuroprotective effects in many neurodegenerative diseases. However, the explicit effect and mechanism of resveratrol on SCI is still unclear. Adenosine 5' monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1), the downstream protein, play key roles in metabolizing of energy, resisting of resistance, and cellular protein homeostasis. In this study, we determined the effects of resveratrol on SCI and their potential relationship with SIRT1/AMPK signaling pathway, autophagy and apoptosis. To determine the effect of resveratrol on SCI recovery, a spinal cord contusion model was employed. Rats received treatment with resveratrol or DMSO immediately following contusion. We determined that Basso, Beattie, and Bresnahan (BBB) scores were significantly higher for injured rats treated with resveratrol. Nissl and HE staining revealed that resveratrol treatment significantly reduced the loss of motor neurons and lesion size in the spinal cord of injured rats when compared to vehicle-treated animals. Spinal cord tissue was assessed by Western blot, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analyses 7 days after injury for changes in expression of SIRT1/AMPK signaling pathway, autophagy and apoptosis proteins. Expression of SIRT1, p-AMPK, Beclin-1, LC3-B, and Bcl-2 was elevated in resveratrol-treated animals, whereas expression of p62, Cleaved Caspase-3, Caspase-9, and Bcl-2 associated X protein (Bax) was inhibited. Immunofluorescence analysis of primary neurons treated with resveratrol alone or in combination with Compound C (AMPK inhibitor) or EX527 (SIRT1 inhibitor) revealed that treatment with the inhibitors blocks the increased LC3-B expression in cells and increases the portion of TUNEL-positive cells. Taken together, these results suggest that resveratrol exerts neuroprotective effects on SCI by regulating autophagy and apoptosis mediated by the SIRT1-AMPK signaling pathway. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.