Chen Zhifeng, Wo Da, Wu Celiang, Ma En, Peng Jinhui, Zhu Weidong, Ren Dan-Ni
Academy of Integrative Medicine, College of Integrative Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Mol Med. 2025 May 6;31(1):172. doi: 10.1186/s10020-025-01240-3.
Spinal cord injury (SCI) is a disability that causes severe traumatic damage to the central nervous system, with increasing prevalence worldwide. Paclitaxel (PTX) is a naturally occurring plant metabolite that has been shown to exhibit various neuroprotective effects in the central nervous system, however, the specific mechanisms underlying its protective effects in SCI remain unclear. In this study, we aimed to explore the therapeutic effects of PTX in SCI, as well as elucidate the underlying molecular mechanisms associated with its neuroprotective potential.
Murine models of spinal cord compression were performed followed by intrathecal administration of corresponding agents for 21 days. Mice were randomly divided into the following four groups: Sham, SCI + Saline, SCI + PTX, and SCI + PTX + XAV939. Recovery of lower limb function and strength, as well as muscular atrophy were examined via multiple scored tests. Degree of neuronal and axonal damage, as well as fibrosis were examined via immunohistochemical staining.
PTX administration significantly improved the recovery of lower limb function and strength, prevented muscular atrophy, as well as decreased the extent of neuronal and axonal death following SCI surgery. PTX also robustly activated the Wnt/β-catenin protein signaling pathway that played a key role in its therapeutic effects. Co-administration with a Wnt/β-catenin pathway inhibitor - XAV939, significantly abolished the beneficial effects of PTX after SCI.
This study provides important new mechanistic insight on the beneficial effects of PTX in protecting against spinal cord injury, as well as the experimental basis for its potential therapeutic use.
脊髓损伤（SCI）是一种导致中枢神经系统严重创伤性损伤的残疾，在全球范围内的患病率呈上升趋势。紫杉醇（PTX）是一种天然存在的植物代谢产物，已被证明在中枢神经系统中具有多种神经保护作用，然而，其在脊髓损伤中发挥保护作用的具体机制仍不清楚。在本研究中，我们旨在探讨紫杉醇对脊髓损伤的治疗作用，并阐明与其神经保护潜力相关的潜在分子机制。
建立脊髓压迫小鼠模型，然后鞘内注射相应药物21天。将小鼠随机分为以下四组：假手术组、脊髓损伤+生理盐水组、脊髓损伤+紫杉醇组和脊髓损伤+紫杉醇+XAV939组。通过多项评分测试检查下肢功能和力量的恢复情况以及肌肉萎缩情况。通过免疫组织化学染色检查神经元和轴突损伤程度以及纤维化程度。
给予紫杉醇显著改善了脊髓损伤手术后下肢功能和力量的恢复，预防了肌肉萎缩，并减少了神经元和轴突死亡的程度。紫杉醇还强烈激活了Wnt/β-连环蛋白信号通路，该通路在其治疗作用中起关键作用。与Wnt/β-连环蛋白通路抑制剂XAV939联合给药显著消除了紫杉醇在脊髓损伤后的有益作用。
本研究为紫杉醇在预防脊髓损伤方面的有益作用提供了重要的新机制见解，也为其潜在治疗用途提供了实验依据。
