| 钭南霖,江丽平,汤敏,金亚玲,陈立辉,蒋晓双,林九洲,陈卫挺.基于Sonic Hedgehog信号通路探讨丹参酮IIA对脊髓损伤大鼠的神经保护机制[J].浙江中西医结合杂志,2025,35(10): |
| 基于Sonic Hedgehog信号通路探讨丹参酮IIA对脊髓损伤大鼠的神经保护机制 |
| Tanshinone IIA Alleviates Spinal Cord Injury in Rats via SHH Signaling Pathway Regulation |
| 投稿时间：2025-05-21 修订日期：2025-08-23 |
| DOI： |
| 中文关键词: 脊髓损伤 丹参酮IIA Sonic Hedgehog信号通路 NF-κB HMGB1 神经炎症 |
| 英文关键词:Spinal cord injury Tanshinone IIA SHH signaling pathway NF-κB HMGB1 Neuroinflammation |
| 基金项目:浙江省自然科学基金(LTGY24H150007)；浙江省医药卫生科技计划项目(2024KY555) |
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| 中文摘要: |
| 目的：探讨丹参酮IIA（Tanshinone IIA, TanIIA）在脊髓损伤（spinal cord injury, SCI）大鼠模型中的神经保护作用，并进一步阐明其是否通过Sonic Hedgehog（SHH）信号通路及NF-κB/HMGB1轴实现对神经炎症的调控。
方法：采用Allen’s打击法建立大鼠T10节段SCI模型，动物随机分为Sham组、SCI组、TanIIA组及TanIIA+SHH抑制剂组（Cyclopamine）。于术后第1、3、5、7天进行BBB评分与Reuter评分评估神经功能恢复；第7天取材，采用HE与尼氏染色观察组织结构变化，免疫荧光及免疫组化评估SHH、p65、HMGB1、Iba1与GFAP的表达与定位，Western blot检测SHH通路关键蛋白（SHH、Smo、Gli1）及NF-κB通路相关蛋白（p65/p-p65、HMGB1）表达水平，ELISA及氧化应激指标反映炎症因子与组织损伤程度。
结果：TanIIA显著改善SCI大鼠的运动与感觉功能，减轻脊髓组织病理损伤，抑制神经元凋亡、炎症因子释放和氧化应激水平。与SCI组相比，TanIIA组中SHH通路相关蛋白（SHH、Smo、Gli1）表达显著升高，小胶质细胞与星形胶质细胞活化水平下降。TanIIA还显著抑制p65磷酸化及核转位，降低神经元中HMGB1表达。联合SHH通路抑制剂后，以上保护作用均明显减弱。
结论：TanIIA可通过激活SHH信号通路，调控NF-κB/HMGB1炎症轴，抑制神经炎症反应与胶质细胞活化，减轻继发性组织损伤，促进神经功能恢复。该研究为TanIIA在SCI治疗中的应用提供了实验依据和理论支持。 |
| 英文摘要: |
Background: Spinal cord injury (SCI) leads to severe neurological deficits and secondary inflammatory responses, with no effective treatment currently available. Tanshinone IIA (TanIIA), a lipid-soluble compound extracted from Salvia miltiorrhiza, has shown neuroprotective potential in central nervous system diseases. This study aimed to investigate the effect of TanIIA on SCI in rats and explore whether its mechanism involves modulation of the Sonic Hedgehog (SHH) signaling pathway and the NF-κB/HMGB1 axis.
Methods: A rat SCI model was established using the modified Allen’s weight-drop method. Rats were divided into four groups: Sham, SCI, TanIIA, and TanIIA+Cyclopamine (SHH pathway inhibitor). Motor and sensory functions were evaluated using the BBB and Reuter scores. Histopathological changes were assessed via HE and Nissl staining. Immunofluorescence and immunohistochemistry were used to detect expression of SHH, p65, HMGB1, Iba1, and GFAP. Western blot analysis was performed to measure SHH pathway proteins (SHH, Smo, Gli1) and inflammatory mediators (p65, p-p65, HMGB1). ELISA and oxidative stress assays were conducted to evaluate inflammatory cytokine levels and tissue damage.
Results: TanIIA significantly improved locomotor function and attenuated pathological damage in SCI rats. It reduced oxidative stress and inflammation, inhibited neuronal apoptosis, and suppressed activation of microglia and astrocytes. TanIIA markedly upregulated SHH, Smo, and Gli1 protein expression, and downregulated p-p65 and HMGB1 levels. SHH activation was also observed in neurons. The protective effects were reversed by Cyclopamine, indicating SHH pathway dependency.
Conclusion: TanIIA exerts neuroprotective effects in SCI by activating the SHH signaling pathway and inhibiting the NF-κB/HMGB1-mediated inflammatory cascade. These findings provide experimental evidence supporting the therapeutic potential of TanIIA in SCI treatment.
Keywords: Spinal cord injury; Tanshinone IIA; SHH signaling pathway; NF-κB; HMGB1; Neuroinflammation
Funding: Zhejiang Provincial Natural Science Foundation of China (LTGY24H150007); Medical and Health Science and Technology Program of Zhejiang (2024KY555) |
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