中国药物警戒 ›› 2026, Vol. 23 ›› Issue (2): 155-161.
DOI: 10.19803/j.1672-8629.20250762

• 基础与临床研究 • 上一篇    下一篇

基于网络药理学与实验验证探讨肌少-骨质疏松大鼠模型发病机制

马宁宁1, 朱琳2△, 冼俊颖1, 冯雪2, 张彩娟2, 王敦方2, 刘海帆2, 刘滨2, 刘鉴瑶2, 李跃华1,3,*, 杨伟鹏2#   

  1. 1南宁市中医医院老年病科，广西 南宁 530001;
    2道地药材品质保障与资源持续利用全国重点实验室，中国中医科学院中药研究所，北京 100700;
    3中国中医科学院西苑医院老年病科，北京 100091
  • 收稿日期:2025-10-31 出版日期:2026-02-15 发布日期:2026-02-13
  • 通讯作者: *李跃华，女，学士，主任医师，教授·博导，中医药防治老年病研究。E-mail: shanzhuyu@126.com; #为共同通信作者。
  • 作者简介:马宁宁，女，硕士，主任医师，中医药防治老年病研究。△为并列第一作者。
  • 基金资助:
    国家重点研发计划（2023YFC3504405）; 广西壮族自治区中医药管理局课题项目（GXZYA-20220337）

Pathogenesis in a Rat Model of Osteosarcopenia Based on Network Pharmacology and Experimental Validation

MA Ningning1, ZHU Lin2△, XIAN Junying1, FENG Xue2, ZHANG Caijuan2, WANG Dunfang2, LIU Haifan2, LIU Bin2, LIU Jianyao2, LI Yuehua1,3,*, YANG Weipeng2#   

  1. 1Department of Geriatrics, Nanning Hospital of Traditional Chinese Medicine, Nanning Guangxi 530001, China;
    2State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;
    3Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
  • Received:2025-10-31 Online:2026-02-15 Published:2026-02-13

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摘要： 目的 结合网络药理学与动物实验探讨肌少-骨质疏松（OS）的分子机制。方法 从多个数据库获取肌少症与骨质疏松症交集靶点，构建蛋白互作网络并筛选核心靶点，进行GO与KEGG富集分析;采用复合方法建立OS大鼠模型，随机分为假手术（Sham）组与去势+地塞米松（OVX+DXM）组。OVX+DXM组每日腹腔注射地塞米松（1 mg·kg-1，连续2周），Sham组给予等量生理盐水。通过苏木精-伊红（HE）染色、Micro-CT及ELISA验证模型后，利用Western Blot检测目标蛋白表达。结果 经过筛选，OS疾病中核心靶基因为INS、IL-6、IL-1β等;GO分析提示OS与肌细胞分化、炎症、凋亡等相关;KEGG分析涉及PI3K/AKT、NF-κB、PPAR等通路。动物实验显示，OVX+DXM组抓力显著下降（P<0.01），血清Irisin、Ca、ALP显著降低（P<0.05），Micro-CT提示骨微结构退化，HE染色显示肌肉排列疏松、骨髓腔扩大;Western Blot显示股骨中OPG、PGC-1α、Runx2、PI3K表达显著降低，PPARγ、RANKL、NF-κB表达显著升高（P<0.05）。结论 OS大鼠模型中PI3K、NF-κB以及PPARγ等蛋白参与了OS发病，其病理进程可能与PI3K/AKT信号通路活性降低导致骨/肌合成不足、NF-κB信号通路激活致使骨吸收/肌蛋白降解加速、PPARγ信号通路活性增加导致骨髓/肌脂肪化有关。

关键词: 网络药理, 肌少-骨质疏松, 发病机制, 实验验证, 信号通路

Abstract: Objective To explore the molecular mechanisms of osteosarcopenia (OS) based on network pharmacology and animal experiments. Methods Common targets of sarcopenia and osteoporosis were identified from multiple databases. A protein-protein interaction network was constructed to screen for hub genes, followed by GO and KEGG enrichment analyses. An OS rat model was established using a combined approach and randomly divided into a sham operation (Sham) group and an ovariectomy plus dexamethasone (OVX+DXM) group. Rats in the OVX+DXM group received daily intraperitoneal injections of dexamethasone (1 mg·kg-1 for 2 weeks) while the Sham group was administered with an equal volume of normal saline. After model validation by HE staining, micro-CT, and ELISA, target protein expressions were determined by Western blot. Results The core hub genes in OS included INS, IL-6, and IL-1β. GO analysis suggested that OS was associated with such biological processes as muscle cell differentiation, inflammation, and apoptosis. KEGG analysis revealed the involvement of PI3K/AKT, NF-κB, and PPAR signaling pathways. Animal experiments showed that in the OVX+DXM group grip strength was significantly reduced (P<0.01), serum levels of irisin, calcium and alkaline phosphatase decreased (P<0.05), bone microstructure deteriorated on micro-CT, muscle fiber arrangement disorganized, and bone marrow cavities enlarged on HE staining. Western blot analysis demonstrated that the expressions of OPG, PGC-1α, Runx2, and PI3K were significantly downregulated while those of PPARγ, RANKL, and NF-κB were significantly upregulated in femoral tissue (P<0.05). Conclusion PI3K, NF-κB, and PPARγ can participate in the pathogenesis of OS, and the pathological process is likely associated with insufficient bone/muscle anabolism caused by reduced activity of the PI3K/AKT signal pathway, accelerated degradation of bone resorption/muscle proteins due to activation of the NF-κB signal pathway, and bone marrow/muscle adipogenesis induced by increased activation of the PPARγ signal pathway.

Key words: Network Pharmacology, Osteosarcopenia, Pathogenesis, Experimental Validation, Signaling Pathway

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