Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Republic of Korea.
Biomed Pharmacother. 2022 Dec;156:113776. doi: 10.1016/j.biopha.2022.113776. Epub 2022 Oct 13.
Lumbar spinal stenosis (LSS) is defined as spinal canal narrowing, resulting in the compression of the nerves traversing the lower back into the leg. Inflammation is the most common cause of LSS. Elevated iron stores are often associated with chronic inflammation resulting in nerve damage-induced pain. Macrophage polarization to either the M1 (inflammatory) or M2 (anti-inflammatory) type is essential for regulating host defenses and promoting tissue repair. However, the precise role of macrophage polarization in iron release or retention in LSS pathophysiology remains elusive. Melittin, a component of bee venom, modulates iron metabolism-related macrophage polarization and is beneficial in LSS. We treated primary peritoneal macrophages with melittin and assessed macrophage polarization by immunofluorescence staining. Melittin (100 and 250 µg/kg) effects on iron deposition-induced macrophage polarization were also evaluated using immunochemistry, real-time PCR, and flow cytometry in an LSS rat model. Locomotor function was assessed using the Basso-Beattie-Bresnahan (BBB) locomotor rating scale, ladder scoring, and von Frey test for up to 3 weeks. Melittin induced M2 polarization of iron-insulted primary macrophages in vitro and increased the proportion of M2 macrophages in the damaged spinal cord in vivo. Moreover, melittin attenuated iron overload-induced M1 polarization by regulating iron metabolism-related genes in rats with LSS. In conclusion, melittin improves locomotor recovery and stimulates axonal growth following LSS. Additionally, it promotes functional recovery in LSS rat models by regulating macrophage iron metabolism, thereby activating M2 macrophages, suggesting its potential application in LSS treatment.
腰椎管狭窄症（LSS）定义为椎管狭窄，导致穿过下背部进入腿部的神经受压。炎症是 LSS 的最常见原因。铁储存升高通常与慢性炎症相关，导致神经损伤引起的疼痛。巨噬细胞向 M1（炎症）或 M2（抗炎）极化对于调节宿主防御和促进组织修复至关重要。然而，巨噬细胞极化在 LSS 病理生理学中铁释放或保留中的精确作用仍然难以捉摸。蜂毒中的一种成分蜂肽调节与铁代谢相关的巨噬细胞极化，对 LSS 有益。我们用蜂肽处理原代腹腔巨噬细胞，并通过免疫荧光染色评估巨噬细胞极化。还使用免疫化学、实时 PCR 和流式细胞术在 LSS 大鼠模型中评估了蜂肽（100 和 250μg/kg）对铁沉积诱导的巨噬细胞极化的影响。使用 Basso-Beattie-Bresnahan（BBB）运动评分量表、梯级评分和 von Frey 测试评估运动功能长达 3 周。蜂肽在体外诱导铁损伤的原代巨噬细胞向 M2 极化，并增加体内受损脊髓中 M2 巨噬细胞的比例。此外，蜂肽通过调节 LSS 大鼠的铁代谢相关基因来减轻铁过载诱导的 M1 极化。总之，蜂肽可改善 LSS 后的运动功能恢复并刺激轴突生长。此外，它通过调节巨噬细胞铁代谢来促进 LSS 大鼠模型的功能恢复，从而激活 M2 巨噬细胞，这表明其在 LSS 治疗中的潜在应用。
