靶向白细胞介素-6信号的活性氧响应性水凝胶促进脊髓损伤后的再生
Targeting Interleukin-6 Signaling with Reactive-Oxygen-Species-Responsive Hydrogel to Promote Regeneration after Spinal Cord Injury.
摘要(中文译文)
脊髓损伤（SCI）会引发过度的炎症反应，其特征是多种炎症因子的上调，从而阻碍神经再生和功能恢复。白细胞介素-6（IL-6）是SCI后损伤灶中观察到的一种早期且关键的炎症介质。拮抗该信号通路是减轻创伤后早期炎症和继发性损伤的一种有前景的策略。在本研究中，我们发现在损伤灶的神经元和小胶质细胞中IL-6受体被特异性激活，表明它们对微环境中早期上调的IL-6信号具有响应性。在体外，中和小胶质细胞中的IL-6信号可有效减轻条件培养基中对神经元轴突生长的抑制作用。在此基础上，我们开发了一种活性氧响应性水凝胶，用于持续局部递送托珠单抗（一种IL-6受体拮抗剂），并将其植入完全横断性SCI模型中。在体内，持续的IL-6受体阻断有效减少了早期炎症细胞浸润，调节小胶质细胞向抗炎表型极化，并促进了损伤灶内的神经元再生。重要的是，该治疗干预促进了SCI小鼠的长期后肢功能恢复。本研究强调了精确靶向早期炎症细胞因子信号通路，特别是IL-6，以改善SCI后结局的治疗潜力。
Abstract
Spinal cord injury (SCI) triggers an excessive inflammatory response, characterized by the up-regulation of various inflammatory factors that impede neural regeneration and functional recovery. Interleukin-6 (IL-6) is an early and critical inflammatory mediator observed in lesions post-SCI. Antagonizing the signaling pathway presents a promising strategy to mitigate early inflammation and secondary injury after trauma. Here, we identified specific activation of the IL-6 receptor in neurons and microglia in lesions, indicating their responsiveness to early up-regulated IL-6 signaling within the microenvironment. In vitro, neutralizing IL-6 signaling in microglia effectively alleviated their inhibitory effects on neuronal axon growth in conditioned media. Building on this, we developed a reactive-oxygen-species-responsive hydrogel for the sustained local delivery of tocilizumab, an IL-6 receptor antagonist, and implanted it in a complete transection SCI model. In vivo, sustained IL-6 receptor blockade effectively reduced early inflammatory cell infiltration, modulated microglial polarization toward an anti-inflammatory phenotype, and fostered neuronal regeneration within the lesion. Importantly, this therapeutic intervention promoted long-term hind limb functional recovery in SCI mice. This study underscores the therapeutic potential of precisely targeting early inflammatory cytokine signaling pathways, particularly IL-6, to improve outcomes after SCI.
如何引用
AMA
Runlin Wen, Xinghui He, Kai Zhang, Wanrong Ma, Zhiquan Yang, Dingyang Liu, et al. Targeting Interleukin-6 Signaling with Reactive-Oxygen-Species-Responsive Hydrogel to Promote Regeneration after Spinal Cord Injury.. Biomaterials research. 2026; doi:10.34133/bmr.0395.
APA
Runlin Wen, Xinghui He, Kai Zhang, Wanrong Ma, Zhiquan Yang, Dingyang Liu, et al (2026). Targeting Interleukin-6 Signaling with Reactive-Oxygen-Species-Responsive Hydrogel to Promote Regeneration after Spinal Cord Injury.. Biomaterials research. https://doi.org/10.34133/bmr.0395
GB/T 7714
Runlin Wen, Xinghui He, Kai Zhang, Wanrong Ma, Zhiquan Yang, Dingyang Liu, et al. Targeting Interleukin-6 Signaling with Reactive-Oxygen-Species-Responsive Hydrogel to Promote Regeneration after Spinal Cord Injury.[J]. Biomaterials research, 2026 doi:10.34133/bmr.0395.
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