| 吴子煜,李皓桓.脉冲电磁场通过抑制软骨细胞铁死亡与炎症缓解骨关节炎进展.骨科,2026,17(3): 248-256. |
| 脉冲电磁场通过抑制软骨细胞铁死亡与炎症缓解骨关节炎进展 |
| Pulsed electromagnetic fields inhibit chondrocyte ferroptosis and inflammation to mitigate osteoarthritis progression |
| 投稿时间：2026-02-12 |
| DOI：10.3969/j.issn.1674-8573.2026.03.009 |
| 中文关键词: 骨关节炎 铁死亡 脉冲电磁场 白细胞介素-1β |
| 英文关键词: Osteoarthritis Ferroptosis Pulsed electromagnetic field IL-1β |
| 基金项目:国家自然科学基金面上项目（12372139） |
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| 中文摘要: |
| 目的 探讨脉冲电磁场（PEMF）通过抑制软骨细胞铁死亡与炎症反应延缓骨关节炎（OA）进展的作用及其机制。方法 采用白细胞介素-1β（IL-1β，10 ng/mL）刺激大鼠软骨细胞建立体外炎症模型，并使用内侧半月板失稳（DMM）手术建立大鼠OA体内模型。体外实验分为对照组、IL-1β诱导组、PEMF处理组（75 Hz，1.5 mT，24 h）及IL-1β联合PEMF处理组。采用CCK-8法检测细胞活力，ELISA法检测前列腺素E2（PGE2）、基质金属蛋白酶1（MMP1）和MMP3水平，Griess法检测一氧化氮（NO）含量，试剂盒检测丙二醛（MDA）、谷胱甘肽（GSH）及铁离子浓度，Western blot检测谷胱甘肽过氧化物酶4（GPX4）、核因子E2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）及核因子κB（NF-κB）通路蛋白表达。通过Nrf2抑制剂ML385及小干扰RNA（siRNA）敲低Nrf2验证信号通路机制。体内实验取材后采用番红O-固绿染色评估软骨组织病理变化。结果 体外实验显示，PEMF显著拮抗IL-1β诱导的软骨细胞活力下降（P＜0.05），降低PGE2、NO、MMP1和MMP3的生成（P＜0.05）。PEMF通过降低MDA及铁离子水平，同时上调GSH、GPX4和铁蛋白表达，有效抑制IL-1β诱导的铁死亡（P＜0.05）。机制研究表明，PEMF显著上调Nrf2及其下游靶点HO-1的表达，并抑制NF-κB通路活化（P＜0.05）。Nrf2抑制剂ML385及Nrf2基因敲低均显著削弱PEMF对炎症和铁死亡的抑制作用（P＜0.05）。体内实验证实，PEMF处理显著改善DMM大鼠关节软骨结构，维持软骨细胞排列整齐。结论 PEMF可通过激活Nrf2信号通路，抑制软骨细胞的炎症反应与铁死亡，进而延缓OA的进展，该策略为OA治疗提供了一种具有临床应用潜力的非侵入性干预手段。 |
| 英文摘要: |
| Objective To investigate the effects and mechanisms of pulsed electromagnetic field (PEMF) on delaying osteoarthritis (OA) progression through inhibiting chondrocyte ferroptosis and inflammatory responses. Methods An in vitro inflammatory model was established using interleukin-1β (IL-1β, 10 ng/mL)-stimulated rat chondrocytes, and an in vivo OA model was induced by destabilization of the medial meniscus (DMM) in rats. In vitro experiments were divided into control group, IL-1β-induced group, PEMF-treated group (75 Hz, 1.5 mT, 24 h), and IL-1β combined with PEMF group. Cell viability was detected by CCK-8 assay. Levels of prostaglandin E2 (PGE2), matrix metalloproteinase 1 (MMP1), and MMP3 were measured by ELISA. Nitric oxide (NO) production was determined by Griess method. Malondialdehyde (MDA), glutathione (GSH), and iron ion concentrations were assessed using commercial kits. Protein expressions of glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nuclear factor-κB (NF-κB) pathway were analyzed by Western blot. The Nrf2 signaling mechanism was validated using Nrf2 inhibitor ML385 and Nrf2 small interfering RNA (siRNA) knockdown. In the in vivo experiment, cartilage tissue was collected and subjected to hematoxylin-eosin staining for evaluation of histopathological changes. Results In vitro results demonstrated that PEMF significantly antagonized IL-1β-induced decrease in chondrocyte viability (P＜0.05) and reduced the production of PGE2, NO, MMP1, and MMP3 (all P＜0.05). PEMF effectively inhibited IL-1β-induced ferroptosis by decreasing MDA and iron ion levels while upregulating GSH, GPX4, and ferritin expressions (all P＜0.05). Mechanistically, PEMF markedly upregulated Nrf2 and its downstream target HO-1, and suppressed NF-κB pathway activation (all P＜0.05). Both pharmacological inhibition of Nrf2 by ML385 and Nrf2 knockdown significantly attenuated the inhibitory effects of PEMF on inflammation and ferroptosis (all P＜0.05). In vivo experiments confirmed that PEMF treatment substantially improved articular cartilage structure and maintained orderly chondrocyte arrangement in DMM rats. Conclusion The results of this study indicate that PEMF can inhibit inflammation and ferroptosis in chondrocytes by activating the Nrf2 signaling pathway, thereby slowing the progression of OA. This strategy provides a non-invasive intervention with clinical application potential for the treatment of OA. |
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