中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (34): 8860-8867.doi: 10.12307/2026.846

• 骨组织构建 bone tissue construction • 上一篇    下一篇

鹤氏唐松草碱干预巨噬细胞极化及破骨细胞活化缓解骨质疏松的作用机制

夏文宇，张  巍，李文豪，江昆龙，吴泽彬，杨惠林   

  1. 苏州大学附属第一医院骨科，江苏省苏州市  215006
  • 收稿日期:2025-10-04 修回日期:2026-01-21 出版日期:2026-12-08 发布日期:2026-04-11
  • 通讯作者: 杨惠林，主任医师，苏州大学附属第一医院骨科，江苏省苏州市 215006
  • 作者简介:第一作者：夏文宇，男，1999年生，江苏省丹阳市人，汉族，硕士，主要从事骨质疏松及骨免疫相关基础研究。
  • 基金资助:
    苏州医学院2023年交叉创新项目，项目负责人：吴泽彬

Mechanism by which Hernandezine alleviates osteoporosis through macrophage polarization and osteoclast activation

Xia Wenyu, Zhang Wei, Li Wenhao, Jiang Kunlong, Wu Zebin, Yang Huilin   

  1. Department of Orthopedics, First Affiliated Hospital of Suzhou University, Suzhou 215006, Jiangsu Province, China
  • Received:2025-10-04 Revised:2026-01-21 Online:2026-12-08 Published:2026-04-11
  • Contact: Yang Huilin, Chief physician, Department of Orthopedics, First Affiliated Hospital of Suzhou University, Suzhou 215006, Jiangsu Province, China
  • About author:Xia Wenyu, MS, Department of Orthopedics, First Affiliated Hospital of Suzhou University, Suzhou 215006, Jiangsu Province, China
  • Supported by:
    2023 Interdisciplinary Innovation Project of Suzhou Medical College (to WZB)

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摘要：


文题释义：
鹤氏唐松草碱(Hernandezine，Her)：是一种从传统中草药金丝马尾连中提取的双苄基异喹啉生物碱，已被证实是一种腺苷酸活化激酶激动剂，具有抗肿瘤、抗血小板凝集和阻断钙离子通道等作用。
巨噬细胞极化：是指巨噬细胞在不同微环境刺激下，通过信号传导途径改变基因表达和功能表型的过程，主要分为经典激活或炎症的M1型和替代激活或抗炎的M2型。

背景：鹤氏唐松草碱因其抗炎生物活性在抗肿瘤、抗血小板凝集和糖尿病等疾病中表现出良好的治疗作用，但它对巨噬细胞表型和破骨细胞活化的影响及其潜在分子机制目前尚不明确。
目的：探讨鹤氏唐松草碱对巨噬细胞极化、破骨细胞活化及骨质疏松症的影响。
方法：①细胞实验：以RAW264.7为巨噬细胞模型，分为4组：空白组、脂多糖组、脂多糖+2.5 μmol/L鹤氏唐松草碱组、脂多糖+5 μmol/L鹤氏唐松草碱组。后3组细胞加入含脂多糖的完全培养基诱导巨噬细胞促炎极化；2个用药组分别加入2.5，5 μmol/L含鹤氏唐松草碱干预。并使用含核因子κB受体活化因子配体的完全培养基诱导RAW264.7细胞向破骨细胞分化，采用qRT-PCR和免疫荧光检测巨噬细胞极化炎症因子的表达，采用qRT-PCR、抗酒石酸酸性磷酸酶染色和F-actin染色评估鹤氏唐松草碱对破骨细胞分化的影响。②体内实验：将24只雌性C57BL/6J小鼠随机分为假手术组、卵巢去势组、卵巢去势+5 mg/kg鹤氏唐松草碱组，卵巢去势+10 mg/kg鹤氏唐松草碱组4组。后3组小鼠切除双侧卵巢构建骨质疏松小鼠模型：2个用药组小鼠术后每2 d分别腹腔注射鹤氏唐松草碱5，10 mg/kg，造模8周后收集股骨进行Micro-CT扫描、骨参数分析和苏木精-伊红染色评估骨质丢失情况。
结果与结论：①鹤氏唐松草碱可以抑制脂多糖诱导的巨噬细胞促炎相关基因表达，其通过下调Toll样受体4/核因子κB信号通路相关基因的转录水平发挥抗炎作用，并呈现出浓度依赖性，其中5 μmol/L鹤氏唐松草碱抑制效果更显著；②鹤氏唐松草碱可以抑制与破骨活化及骨吸收相关基因的表达，抑制体外破骨细胞活化，同样呈浓度依赖性；③鹤氏唐松草碱可以减少雌激素缺乏性骨质疏松小鼠的骨质流失，10 mg/kg鹤氏唐松草碱治疗组恢复效果更好；④结论：研究证实了鹤氏唐松草碱抑制巨噬细胞促炎表型的转化过程和抑制破骨细胞活化过程，是通过下调Toll样受体4/核因子κB信号通路发挥抗炎作用；并证实鹤氏唐松草碱可以减轻雌激素缺乏性骨质疏松的过量骨丢失。 
https://orcid.org/0009-0001-5946-9212(夏文宇)


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 鹤氏唐松草碱, 巨噬细胞, 炎症, 破骨细胞活化, 骨质疏松

Abstract: BACKGROUND: Hernandezine has shown promising therapeutic effects due to its anti-inflammatory bioactivity in diseases such as suppression of tumors, antiplatelet agglutination and diabetes. However, there are no basic studies on the effects and molecular mechanism of Hernandezine on macrophage phenotype and osteoclast activation.
OBJECTIVE: To investigate the role of Hernandezine on the regulation of macrophage polarization, osteoclast activation and osteoporosis.
METHODS: (1) Cellular experiments: RAW264.7 was used as macrophage model and divided into four groups: Control group, lipopolysaccharide group, lipopolysaccharide + 2.5 μmol/L Hernandezine group, lipopolysaccharide + 5 μmol/L Hernandezine group. Macrophage polarization was induced in the latter three groups using a complete medium supplemented with lipopolysaccharide. The two drug-treated groups received 2.5 and 5 μmol/L Hernandezine, respectively. RAW264.7 cells were induced toward osteoclast differentiation using a complete medium supplemented with nuclear factor κB receptor activator ligand. Macrophage polarization was assessed via qRT-PCR and immunofluorescence for inflammatory cytokine expression. The effects of Hernandezine on osteoclast differentiation were evaluated using qRT-PCR, tartrate-resistant acid phosphatase staining, and F-actin staining. (2) In vivo experiments: Twenty-four 8-week-old female C57BL/6J mice were randomly divided into four groups: sham-operated group, ovarian extirpation group, 5 mg/kg Hernandezine group and 10 mg/kg Hernandezine group. Bilateral ovariectomy was performed to establish an osteoporosis mouse model in the latter three groups. Hernandezine at the dose of 5 and 10 mg/kg was intraperitoneally injected in the two drug-treated groups every 2 days after the operation. Femurs were collected after 8 weeks of modeling for Micro-CT scanning, bone parameter analysis and hematoxylin-eosin staining to assess bone loss.
RESULTS AND CONCLUSION: (1) Hernandezine could inhibit the expression of pro-inflammatory related genes induced by lipopolysaccharide, and exerted anti-inflammatory effects by down-regulating the transcription level of genes related to Toll-like receptor 4/nuclear factor-κB signaling pathway in a concentration-dependent manner. 5 μmol/L Hernandezine exhibited a more pronounced inhibitory effect. (2) Hernandezine could inhibit the expression of genes related to osteoclast activation and bone resorption, and inhibit osteoclast activation in vitro, also in a concentration-dependent manner. (3) Hernandezine could reduce bone loss in estrogen-deficient induced osteoporosis mice, and the recovery effect was more significant in the 10 mg/kg group. In conclusion, we confirmed that Hernandezine inhibits the conversion process of macrophage pro-inflammatory phenotype and osteoclast activation, and exerts anti-inflammatory effects by down-regulating the Toll-like receptor 4/nuclear factor-κB signaling pathway. Hernandezine has also been confirmed to attenuate excessive bone loss in estrogen-deficient osteoporosis.  


Key words: Hernandezine, macrophages, inflammation, osteoclast activation, osteoporosis

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