中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (18): 4568-4581.doi: 10.12307/2026.744

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

鹿角胶调控肠道菌群-胆汁酸代谢通路改善激素性股骨头坏死模型大鼠的机制

柴金莲1，梁学振2，3，孙铁锋4，李树栋2，李  威2，李广政2，于华芸1，王  平4   

  1. 1山东中医药大学中医学院，山东省济南市  250355；2山东中医药大学第一临床医学院，山东省济南市  250014；3山东中医药大学附属医院显微骨科，山东省济南市  250014；4山东省中医药研究院，山东省济南市  250014
  • 收稿日期:2025-06-20 接受日期:2025-09-12 出版日期:2026-06-28 发布日期:2025-12-01
  • 通讯作者: 于华芸，博士，教授，博士生导师，山东中医药大学中医学院，山东省济南市 250355 通讯作者：王平，博士，研究员，博士生导师，山东省中医药研究院，山东省济南市 250014
  • 作者简介:柴金莲，女，1990年生，山东省滨州市人，汉族，在读博士，主要从事方剂学、中药药理学的研究。
  • 基金资助:
    山东省重点研发计划(科技示范工程)(2021SFGC1205)，项目负责人：王平；山东省技术创新引导计划(中央引导地方科技发展基金)(YDZX2024122)，项目负责人：王平；国家自然科学基金资助项目(82205154)，项目负责人：梁学振；山东省自然科学基金面上项目(ZR2024MH156)，项目负责人：梁学振；山东省中医药科技面上项目(MR20241837)，项目负责人：梁学振

Mechanistic insights into how Cervi Cornus Colla regulates the intestinal flora-bile acid metabolic pathway to alleviate steroid-induced osteonecrosis of the femoral head in a rat model 

Chai Jinlian1, Liang Xuezhen2, 3, Sun Tiefeng4, Li Shudong2, Li Wei2, Li Guangzheng2, Yu Huayun1, Wang Ping4   

  1. 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China; 2First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China; 3Department of Orthopedic Microsurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China; 4Shandong Provincial Research Institute of Traditional Chinese Medicine, Jinan 250014, Shandong, China 
  • Received:2025-06-20 Accepted:2025-09-12 Online:2026-06-28 Published:2025-12-01
  • Contact: Yu Huayun, PhD, Professor, Doctoral supervisor, College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China Co-corresponding author:Wang Ping, PhD, Investigator, Doctoral supervisor, Shandong Provincial Research Institute of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China
  • About author:Chai Jinlian, PhD candidate, College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China
  • Supported by:
    Shandong Provincial Key Research and Development Program (Science and Technology Demonstration Project), No. 2021SFGC1205 (to WP); Shandong Provincial Technology Innovation Guidance Program (Central Government Guides Local Science and Technology Development Fund), No. YDZX2024122 (to WP); the National Natural Science Foundation of China, No. 82205154 (to LXZ); Shandong Provincial Natural Science Foundation General Program, No. ZR2024MH156 (to LXZ); Shandong Provincial Traditional Chinese Medicine Science and Technology General Program, No. MR20241837 (to LXZ)

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摘要：


文题释义：
肠-骨轴：是指肠道(特别是其微生物群落)与骨骼系统之间存在的双向通信网络。肠道菌群及其产生的代谢物(如短链脂肪酸、胆汁酸)可通过血液循环抵达骨骼，作用于骨细胞上的特定受体，从而调控骨形成、骨吸收及炎症反应，维持骨骼代谢平衡。这一轴线的紊乱与多种骨病(如骨质疏松、骨坏死)的发生密切相关。
胆汁酸代谢通路：肝脏利用胆固醇合成初级胆汁酸(胆酸、鹅脱氧胆酸)，进食后排入肠道协助脂质消化。肠道菌群通过去结合和7α-脱羟基作用，将初级胆汁酸转化为次级胆汁酸(脱氧胆酸、石胆酸)，约95%胆汁酸经肠肝循环重吸收，其余随粪便排出。该通路不仅调节脂质吸收，其产物(尤其次级胆汁酸)还可作为关键的信号分子，通过激活全身多种组织(如肠道、肝脏、脂肪、骨骼)的法尼醇X受体(FXR)、G蛋白偶联受体5(TGR5)，广泛调控糖脂代谢、能量消耗、炎症反应及骨代谢平衡。

背景：鹿角胶含有的核心蛋白聚糖等成分可入骨，调节肠道菌群及胆汁酸代谢，经肠 - 骨轴信号传导，在改善激素性股骨头坏死的骨代谢异常中具有潜在价值。
目的：验证鹿角胶对激素性股骨头坏死模型大鼠的干预作用及其通过“肠-骨轴”发挥保护作用的潜在机制。
方法：30只SD大鼠随机分为对照组、模型组和鹿角胶组，后2组大鼠每周前3 d臀肌注射甲泼尼龙琥珀酸钠，持续3周，诱导激素性股骨头坏死模型。鹿角胶组大鼠同期开始给予鹿角胶灌胃，对照组、模型组灌胃等体积纯净水，连续干预6周。使用苏木精-伊红和Masson染色观察股骨头病理学变化；ELISA法检测血清白细胞介素1β水平；Western blot法检测股骨头Runt相关转录因子2和Ⅰ型胶原a1蛋白表达；16SrDNA测序分析肠道菌群多样性，并结合前期粪便代谢组学数据进行联合分析。
结果与结论：①与模型组相比，鹿角胶干预显著降低了股骨头空骨陷窝率和脂肪细胞浸润，增加胶原纤维含量并改善骨小梁结构(P < 0.05)，显著下调大鼠血清白细胞介素1β水平，并上调股骨头Runt相关转录因子2和Ⅰ型胶原a1蛋白的表达(P < 0.05)。②肠道菌群分析显示，与模型组相比，鹿角胶干预在门水平降低了Firmicutes的相对丰度；在属水平上显著改变了Candidatus_Saccharimonas、Turicibacter、Fusobacterium和UCG_007等菌属的丰度。③Spearman相关性分析表明，Candidatus_Saccharimonas与Β-鼠胆酸、胆酸和胆汁酸呈正相关，而Turicibacter、Fusobacterium和UCG_007分别与Β-鼠胆酸、胆酸及牛磺酸呈负相关。④KEGG通路富集分析进一步揭示，次级胆汁酸生物合成、初级胆汁酸生物合成及牛磺酸代谢通路显著富集(P < 0.05)。⑤结果说明，鹿角胶可能通过调控肠道菌群及其相关代谢物，影响胆汁酸和牛磺酸代谢通路，缓解糖皮质激素诱导的股骨头损伤。                                            
https://orcid.org/0009-0009-5134-8721(柴金莲)

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: 鹿角胶, 激素性股骨头坏死, 肠-骨轴, 肠道菌群, 胆汁酸代谢

Abstract: BACKGROUND: Cervi Cornus Colla, which contains bioactive proteoglycans and other bone-targeting components, demonstrates therapeutic potential by modulating gut microbiota composition and bile acid metabolism. Through the gut-bone axis signaling pathway, Cervi Cornus Colla effectively ameliorates bone metabolic disorders associated with steroid-induced osteonecrosis of the femoral head.
OBJECTIVE: To investigate the intervention effect of Cervi Cornus Colla on steroid-induced osteonecrosis of the femoral head in rat models and its potential protective mechanism through the "gut-bone axis."
METHODS: Thirty Sprague-Dawley rats were randomly divided into three groups: control, model and Cervi Cornus Colla treatment groups. To establish a steroid-induced osteonecrosis of the femoral head  model, rats in the model and Cervi Cornus Colla groups received intramuscular gluteal injections of methylprednisolone sodium succinate during the first 3 days of each week for 3 consecutive weeks. Concurrently, the rats in the Cervi Cornus Colla group were administered Cervi Cornus Colla via oral gavage, and those in the control group and the model group received equal volume of purified water via oral gavage for 6 consecutive weeks. Pathological changes in the femoral head were evaluated using hematoxylin-eosin and Masson staining. The serum interleukin-1β level was detected by ELISA. Western blot analysis assessed the expression of Runt-related transcription factor 2 and type I collagen a1 protein in the femoral head. Gut microbiota diversity was analyzed via 16SrDNA sequencing, and integrated with prior fecal metabolomics data to explore potential mechanistic correlations.
RESULTS AND CONCLUSION: (1) Compared with the model group, Cervi Cornus Colla significantly reduced empty lacunae rate and adipocyte infiltration, increased collagen fiber content and improved trabecular bone structure (P < 0.05). Additionally, Cervi Cornus Colla markedly downregulated serum interleukin-1β levels and upregulated Runt-related transcription factor 2 and type I collagen a1 protein expressions (P < 0.05). (2) Gut microbiota analysis revealed that compared with the model group, Cervi Cornus Colla intervention significantly reduced the relative abundance of Firmicutes at the phylum level and markedly altered the abundances of Candidatus_Saccharimonas, Turicibacter, Fusobacterium, and UCG_007 at the genus level. (3) Spearman correlation analysis showed that Candidatus_Saccharimonas was positively correlated with β-muricholic acid, cholic acid, and bile acids, while Turicibacter, Fusobacterium, and UCG_007 were negatively correlated with β-muricholic acid, cholic acid, and taurine. (4) Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis further revealed significant enrichment in secondary bile acid biosynthesis, primary bile acid biosynthesis, and taurine metabolism pathways (P < 0.05). To conclude, Cervi Cornus Colla may alleviate glucocorticoid-induced femoral head injury by regulating gut microbiota and its related metabolites, thereby influencing bile acid and taurine metabolic pathways.

Key words: Cervi Cornus Colla, steroid-induced osteonecrosis of the femoral head, gut-bone axis, gut microbiota, bile acid metabolism

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