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AMPK/SIRT1 通路参与曲克芦丁对 CCI 诱导的神经病理性疼痛的抗镇痛作用。

Involvement of AMPK/SIRT1 pathway in anti-allodynic effect of troxerutin in CCI-induced neuropathic pain.

机构信息

Department of Anesthesiology, Hunan Provincial Maternal and Child Health Hospital, Changsha 410000, Hunan Province, China.

Department of Anesthesiology, Hunan Provincial Maternal and Child Health Hospital, Changsha 410000, Hunan Province, China.

出版信息

Eur J Pharmacol. 2015 Dec 15;769:234-41. doi: 10.1016/j.ejphar.2015.11.023. Epub 2015 Nov 18.

Abstract

Neuropathic pain was regarded as a main form of chronic pain condition that remains difficult to treat. Conventional pharmacotherapy for neuropathic pain responsed vary and side effects limited their compliance. These prompted us to find new alternatives. In this study, we investigated the effect of troxerutin on treatment of CCI-induced neuropathic pain. Results showed that troxerutin significantly reversed mechanical allodynia and thermal hyperalgesia. In L4-6 spinal cord, troxerutin reduced the expression of INF-γ, IL-1β, TNF-α, and activation of NF-κB(p65). Immunofluorescence results showed that troxerutin significantly inhibited microglia activation induced by CCI surgery. Further, troxerutin treatment significantly induced AMPK activation and inhibited CCI-induced SIRT1 decrease. However, AMPK inhibitor compound C and SIRT1 inhibitor EX527 inhibited analgesic effect of troxerutin in CCI mice. This demonstrated the involvement of AMPK/SIRT1 pathway in anti-allodynic effect of troxerutin in CCI mice. Troxerutin could be developed as a potential therapeutic agent for neuropathic pain.

摘要

神经病理性疼痛被认为是一种主要的慢性疼痛病症,仍然难以治疗。神经病理性疼痛的常规药物治疗反应各不相同,副作用也限制了其依从性。这促使我们寻找新的替代方法。在这项研究中,我们研究了曲克芦丁对 CCI 诱导的神经病理性疼痛的治疗效果。结果表明,曲克芦丁能显著逆转机械性痛觉过敏和热痛觉过敏。在 L4-6 脊髓中,曲克芦丁降低了 INF-γ、IL-1β、TNF-α 的表达和 NF-κB(p65)的激活。免疫荧光结果表明,曲克芦丁能显著抑制 CCI 手术引起的小胶质细胞激活。此外,曲克芦丁治疗可显著诱导 AMPK 激活,并抑制 CCI 诱导的 SIRT1 减少。然而,AMPK 抑制剂化合物 C 和 SIRT1 抑制剂 EX527 抑制了曲克芦丁在 CCI 小鼠中的镇痛作用。这表明 AMPK/SIRT1 通路参与了曲克芦丁在 CCI 小鼠中的抗痛觉过敏作用。曲克芦丁可能被开发为治疗神经病理性疼痛的潜在治疗剂。

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