Zheng Kesong, Yang Chengwei, Han Mingming, Kang Fang, Li Juan
Cheeloo College of Medicine, Shandong University, Jinan City, Shandong Province, China; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
Phytomedicine. 2025 Sep;145:157000. doi: 10.1016/j.phymed.2025.157000. Epub 2025 Jun 19.
Bone cancer pain (BCP) remains a significant clinical challenge with poorly understood mechanisms. While Th17 and Treg cells have been implicated in pain pathways, their specific roles in BCP pathogenesis require further investigation. Salidroside (SAL), a natural compound with anti-inflammatory properties, shows potential for pain management but its mechanism in BCP is unclear.
This study aimed to investigate SAL's analgesic effects in BCP and elucidate its mechanism of action through the AMPK/SIRT1 pathway and Th17/Treg cell regulation.
Experimental animal study using a well-established BCP mouse model with pharmacological interventions and cellular/molecular analyses.
C57BL/6 mice were used to establish a BCP model via tumor cell implantation. Behavioral tests assessed mechanical allodynia and thermal hyperalgesia. Flow cytometry analyzed spinal cord Th17/Treg populations, while Western blotting evaluated AMPK/SIRT1 pathway proteins. Pharmacological interventions included SAL administration, IL-17 neutralization, and AMPK/SIRT1 pathway modulation.
SAL treatment significantly alleviated pain behaviors in BCP mice (p < 0.01). Cellular analyses revealed SAL restored Th17/Treg balance by reducing Th17 markers (IL-17, RORγt, p-STAT3) and increasing Treg markers (FOXP3, p-STAT5). SAL activated the AMPK/SIRT1 pathway, while pathway inhibitors reversed SAL's therapeutic effects, confirming the mechanism.
SAL effectively alleviates BCP by modulating Th17/Treg cell differentiation through AMPK/SIRT1 pathway activation. These findings suggest SAL's potential as a novel immunomodulatory therapy for BCP management.
骨癌疼痛（BCP）仍然是一个重大的临床挑战，其机制尚不清楚。虽然Th17细胞和调节性T细胞（Treg）与疼痛通路有关，但其在BCP发病机制中的具体作用仍需进一步研究。红景天苷（SAL）是一种具有抗炎特性的天然化合物，显示出在疼痛管理方面的潜力，但其在BCP中的作用机制尚不清楚。
本研究旨在探讨SAL对BCP的镇痛作用，并通过AMPK/SIRT1通路和Th17/Treg细胞调节阐明其作用机制。
使用成熟的BCP小鼠模型进行实验动物研究，并进行药理学干预和细胞/分子分析。
采用C57BL/6小鼠通过肿瘤细胞植入建立BCP模型。行为测试评估机械性异常性疼痛和热痛觉过敏。流式细胞术分析脊髓Th17/Treg细胞群，蛋白质免疫印迹法评估AMPK/SIRT1通路蛋白。药理学干预包括给予SAL、中和白细胞介素-17（IL-17）以及调节AMPK/SIRT1通路。
SAL治疗显著减轻了BCP小鼠的疼痛行为（p<0.01）。细胞分析显示，SAL通过降低Th17标志物（IL-17、维甲酸相关孤儿受体γt、磷酸化信号转导和转录激活因子3）和增加Treg标志物（叉头盒蛋白P3、磷酸化信号转导和转录激活因子5）恢复了Th17/Treg平衡。SAL激活了AMPK/SIRT1通路，而该通路抑制剂逆转了SAL的治疗效果，证实了其作用机制。
SAL通过激活AMPK/SIRT1通路调节Th17/Treg细胞分化，有效减轻BCP。这些发现表明SAL作为一种新型免疫调节疗法用于BCP管理具有潜力。
