Carnosic acid attenuates neuropathic pain in rat through the activation of spinal sirtuin1 and down-regulation of p66shc expression
Carnosic acid attenuates neuropathic pain in rat through the activation of spinal sirtuin1 and down-regulation of p66shc expression
复制标题
鼠尾草酸通过激活脊髓 Sirtuin1 和下调 p66shc 表达减轻大鼠神经性疼痛
DOI：
10.1016/j.neuint.2016.01.004
复制
发表时间：
2016-02-01
影响因子：
4.2
通讯作者：
Wang, Jun-lu
中科院分区：
文献类型：
--
作者：
Chen, Shuang-dong;Ji, Bin-bin;Wang, Jun-lu
背景：研究表明，鼠尾草酸具有保肝、抗氧化、抗炎等多种生物活性。然而，鼠尾草酸在神经病理性疼痛中的作用尚不清楚。方法：建立成年雄性SD大鼠慢性缩窄性损伤(CCI)神经病理性疼痛模型。记录大鼠机械戒断阈值(MWT)和热戒断潜伏期(TWL)，并用免疫印迹法检测Sirtuin1和p66shc的含量。结果：鞘内注射鼠尾草酸可减轻慢性缩窄性损伤后大鼠的机械痛敏和热痛敏。有趣的是，鼠尾草酸的镇痛作用与脊髓Sirtuin1的激活呈正相关；然而，脊髓中的鼠尾草酸对p66shc有抑制作用。此外，Sirtuin1抑制剂EX-527可逆转肉桂酸的抗伤害性作用。结论：肉桂酸对CCI诱导的疼痛有较好的治疗作用。鼠尾草酸激活脊髓Sirtuin1可能通过下调p66shc的表达来减轻神经病理性疼痛。(C)2016爱思唯尔有限公司。保留所有权利。
Background: It has been reported that carnosic acid (CA) exhibits a range of biological activities including hepatoprotective, antioxidant and anti-inflammatory. However, the effect of carnosic acid in neuropathic pain remained elusive.Methods: A neuropathic pain model of chronic constriction injury (CCI) was established in adult male Sprague-Dawley rats. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded, and western blot was performed to detect sirtuin1 and p66shc content.Results: Intrathecal administration of carnosic acid attenuated mechanical allodynia and thermal hyperalgesia in rats following chronic constriction injury. Interestingly, carnosic acid analgesic effect was positively associated with spinal sirtuin1 activation; however, p66shc was inhibited by carnosic acid in the spinal cord. In additional, sirtuin1 inhibitor EX-527 reversed the anti-nociceptive effect of carnosic acid.Conclusions: Carnosic acid is effective in the treatment of the established CCI-induced pain. It may be possible that spinal sirtuin1 activition by carnosic acid attenuates neuropathic pain through a mechanism involving the down-regulation of p66shc expression. (C) 2016 Elsevier Ltd. All rights reserved.