1 Department of Anesthesiology, Hunan Provincial Maternal and Child Health Hospital, Changsha, China.
2 Department of Endocrinology, Yongzhou-Affiliated Hospital of University of South China, Yongzhou, China.
Mol Pain. 2018 Jan-Dec;14:1744806918768970. doi: 10.1177/1744806918768970.
Background One of the most common side effects of paclitaxel was dosage-dependently painful neuropathy. Various reports indicated that spinal neuroinflammation was involved in paclitaxel-induced neuropathic pain. This study investigated the effect of icariin on paclitaxel-induced neuroinflammation and peripheral neuropathy in rats. Methods Two parts were included in this study. In part one, the effect of icariin on paclitaxel-induced neuropathic pain was investigated. Mechanical thresholds were measured as primary outcomes. Production of proinflammatory factors (tumor necrosis factor-α, interleukin-1 β, and interleukin-6), activation of nuclear factor-κB (NF-κB(p65)) signal, and activation of astrocytes were detected as secondary outcomes. Spinal Sirtuin 1 (SIRT1) expression, H4 acetylation, and NAD content were measured to investigate the effect of icariin on spinal SIRT1 signal pathway. In part two, the role of SIRT1 signal on icariin-induced effect in rats was investigated, and EX527, a SIRT1 inhibitor, was employed. Results The results showed paclitaxel treatment induced significant decrease in mechanical thresholds. Paclitaxel treatment also induced NF-κB(p65) activation and upregulation of proinflammatory factors (TNF-α, IL-1β, and IL-6). Paclitaxel also induced astrocyte activation in the spinal cord. However, 100 mg/kg icariin treatment significantly alleviated paclitaxel-induced mechanical allodynia and spinal neuroinflammation. Furthermore, icariin treatment dosage-dependently reversed paclitaxel-induced SIRT1 downregulation and H4 acetylation. EX527, a selective SIRT1 inhibitor, completely reversed icariin-induced anti-neuroinflammation and anti-allodynia effects in paclitaxel-induced neuropathic pain rats. Conclusions This meant that spinal SIRT1 activation was involved in icariin-induced effects in paclitaxel-induced neuropathic pain rats. Icariin could be a potential agent for the treatment of paclitaxel-induced neuropathic pain.
紫杉醇最常见的副作用之一是剂量依赖性的痛性神经病。各种报道表明，脊髓神经炎症参与了紫杉醇诱导的神经性疼痛。本研究探讨了淫羊藿苷对紫杉醇诱导的大鼠神经炎症和周围神经病的影响。
本研究包括两部分。在第一部分中，研究了淫羊藿苷对紫杉醇诱导的神经性疼痛的影响。机械阈值作为主要结果进行测量。同时检测促炎因子（肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6）的产生、核因子-κB（NF-κB(p65)）信号的激活以及星形胶质细胞的激活情况。测量脊髓 Sirtuin 1（SIRT1）表达、H4 乙酰化和 NAD 含量，以研究淫羊藿苷对脊髓 SIRT1 信号通路的影响。在第二部分中，研究了 SIRT1 信号对淫羊藿苷诱导大鼠作用的影响，并使用了 SIRT1 抑制剂 EX527。
结果表明，紫杉醇治疗导致机械阈值明显降低。紫杉醇治疗还诱导了 NF-κB(p65)的激活和促炎因子（TNF-α、IL-1β和 IL-6）的上调。紫杉醇还诱导了脊髓中的星形胶质细胞激活。然而，100mg/kg 淫羊藿苷治疗显著缓解了紫杉醇诱导的机械性痛觉过敏和脊髓神经炎症。此外，淫羊藿苷治疗剂量依赖性地逆转了紫杉醇诱导的 SIRT1 下调和 H4 乙酰化。选择性 SIRT1 抑制剂 EX527 完全逆转了淫羊藿苷诱导的 SIRT1 抑制剂在紫杉醇诱导的神经性疼痛大鼠中的抗神经炎症和抗痛觉过敏作用。
这意味着脊髓 SIRT1 的激活参与了淫羊藿苷在紫杉醇诱导的神经性疼痛大鼠中的作用。淫羊藿苷可能是治疗紫杉醇诱导的神经性疼痛的潜在药物。
