中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (29): 7512-7519.doi: 10.12307/2026.251

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

股骨头坏死愈胶囊缓解激素性股骨头坏死大鼠外周痛觉敏化的机制

成  彦，阳一丹，李志鹏，刘又文，郭珈宜，岳  辰   

  1. 河南省洛阳正骨医院(河南省骨科医院)，河南省洛阳市   471002

  • 收稿日期:2025-09-03 修回日期:2025-11-20 出版日期:2026-10-18 发布日期:2026-03-02
  • 通讯作者: 郭珈宜，主任医师，河南省洛阳正骨医院(河南省骨科医院)，河南省洛阳市 471002 通讯作者：岳辰，副主任医师，河南省洛阳正骨医院(河南省骨科医院)，河南省洛阳市 471002
  • 作者简介:成彦，女，1986年生，河南省洛阳市人，汉族，硕士，医药工程师，主要从事骨科药品及器械研发工作。 共同第一作者：阳一丹，女，1998年生，河南省三门峡市人，汉族，硕士，医师，主要从事中医药防治骨关节病与运动损伤研究。
  • 基金资助:
    国家自然科学基金面上项目(82074472)“基于TLR4-MyD88-NF-κB信号通路探讨补肾活血法促M2极化干预激素性股骨头坏死的骨免疫机制”，项目负责人：刘又文；河南省中医药研究专项项目(2024ZY1023)“并针疗法对膝骨关节炎疼痛的影响及机制探究”，项目负责人：郭珈宜

Mechanism of Gugutou Huaisiyu Capsule in alleviating peripheral pain sensitization in rats with steroid-induced osteonecrosis of the femoral head

Cheng Yan, Yang Yidan, Li Zhipeng, Liu Youwen, Guo Jiayi, Yue Chen   

  1. Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang 471002, Henan Province, China
  • Received:2025-09-03 Revised:2025-11-20 Online:2026-10-18 Published:2026-03-02
  • Contact: Guo Jiayi, Chief physician, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang 471002, Henan Province, China Co-corresponding author: Yue Chen, Associate chief physician, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang 471002, Henan Province, China
  • About author:Cheng Yan, MS, Pharmaceutical engineer, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang 471002, Henan Province, China Yang Yidan, MS, Physician, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang 471002, Henan Province, China Cheng Yan and Yang Yidan contributed equally to this work.
  • Supported by:
    The National Natural Science Foundation of China, No. 82074472 (to LYW); Henan Provincial Special Project on Traditional Chinese Medicine Research, No. 2024ZY1023 (to GJY).

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摘要：



文题释义：
酪氨酸激酶受体A：是一种高亲和力的神经生长因子受体，在痛觉信号传递、神经元发育分化及突触可塑性等生理过程中发挥关键作用。酪氨酸激酶受体A异常激活或表达可能与某些肿瘤、疼痛感知异常及神经退行性疾病相关。
痛觉敏化：是指机体神经元兴奋性升高、突触传递增强等导致机体对疼痛的感知阈值降低、反应性增强，是慢性疼痛发生发展的重要机制之一。

背景：前期研究证明，股骨头坏死愈胶囊能够有效缓解股骨头坏死患者的疼痛症状，但作用机制仍不明确。
目的：探讨股骨头坏死愈胶囊缓解激素性股骨头坏死大鼠外周痛觉敏化的作用机制。
方法：将32只SD大鼠随机分4组干预：除空白对照组(n=8)外，模型组(n=8)、低剂量中药组(n=8)和高剂量中药组(n=8)大鼠采用腹腔注射脂多糖联合臀肌注射甲泼尼松龙构建激素性股骨头坏死模型，造模7 d后，低、高剂量中药组分别灌胃给予0.33，0.67 g/kg的股骨头坏死愈胶囊煎剂，空白对照组、模型组灌胃给予生理盐水，每天1次，连续给药8周。末次给药结束后，Micro-CT分析股骨头松质骨微结构，
Von-Frey test检测大鼠机械性疼痛阈值，Elisa法检测大鼠血清中疼痛介质降钙素基因相关肽、P物质的表达，多重免疫荧光染色、实时定量PCR检测股骨头及背根神经节中酪氨酸激酶受体A、降钙素基因相关肽、神经元标志物β3-微管蛋白的蛋白及基因表达。
结果与结论：①Micro-CT及疼痛行为学检测显示，与空白对照组比较，模型组大鼠股骨头松质骨微结构破坏明显，骨密度、骨体积分数下降，骨小梁分离度升高，机械痛阈值降低；与模型组比较，低、高剂量中药组大鼠骨小梁结构显著改善，骨密度、骨体积分数升高，骨小梁分离度下降，机械痛阈值升高。②Elisa检测显示，模型组降钙素基因相关肽、P物质水平较空白对照组显著升高，低、高剂量中药组降钙素基因相关肽、P物质水平较模型组降低。③多重免疫荧光染色与实时定量PCR检测显示，与空白对照组比较，模型组大鼠股骨头及背根神经节中降钙素基因相关肽、酪氨酸激酶受体A、β3-微管蛋白的蛋白及基因表达均升高；与模型组比较，低、高剂量中药组大鼠股骨头及背根神经节中降钙素基因相关肽、酪氨酸激酶受体A、β3-微管蛋白的蛋白及基因表达均降低。④结果表明，股骨头坏死愈胶囊能够提高激素性股骨头坏死模型大鼠的机械痛阈值、抑制神经元异常活化、缓解痛觉敏化，该机制可能与抑制酪氨酸激酶受体A相关。

https://orcid.org/0009-0009-5375-6251 (成彦) 

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: 激素性股骨头坏死, 股骨头坏死愈胶囊, 酪氨酸激酶受体A, 痛觉敏化, 骨坏死, 组织构建

Abstract: BACKGROUND: Previous studies have demonstrated that Gugutou Huaisiyu Capsule effectively alleviate pain in patients with osteonecrosis of femoral head; however, the mechanism of action remains unclear.
OBJECTIVE: To investigate the mechanism by which Gugutou Huaisiyu Capsule mitigate peripheral pain sensitization in rats with steroid-induced osteonecrosis of the femoral head.
METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to four groups: blank control, model, low-dose Gugutou Huaisiyu Capsule, and high-dose Gugutou Huaisiyu Capsule groups with eight rats in each group. Steroid-induced femoral head necrosis rat models were established via intraperitoneal injection of lipopolysaccharide combined with gluteal injection of methylprednisolone in the later three groups. Seven days post-modeling, rats in the low- and high-dose Gugutou Huaisiyu Capsule groups received intragastric administration of 0.33 g/kg and 0.67 g/kg of the decoction, respectively, while the blank control and model groups received intragastric administration of saline once daily for 8 consecutive weeks. Following the final administration, trabecular bone microarchitecture in the femoral head was assessed using micro-CT analysis. The mechanical pain thresholds were measured with the Von Frey test. Serum levels of pain mediators calcitonin gene-related peptide and substance P were detected using ELISA. Multiplex immunofluorescence staining and real-time quantitative PCR were used to detect the protein and gene expression of tyrosine kinase receptor A, calcitonin gene-related peptide, and neuronal marker β3-tubulin in the femoral head and dorsal root ganglion.
RESULTS AND CONCLUSION: (1) Micro-CT and pain behavioral tests revealed that compared with the blank control group, significant destruction of trabecular bone microarchitecture in the femoral head, decreased bone density and bone volume fraction, increased trabecular separation, and reduced mechanical pain threshold are found in the model group. Compared with the model group, trabecular structure significantly improved, bone mineral density and bone volume fraction significantly increased, trabecular separation significantly decreased, and mechanical pain threshold significantly elevated in the low- and high-dose Gugutou Huaisiyu Capsule groups. (2) ELISA analysis revealed calcitonin gene-related peptide and substance P levels were significantly increased in the model group compared with the blank control group, while calcitonin gene-related peptide and substance P levels were significantly decreased in the low- and high-dose Gugutou Huaisiyu Capsule groups compared with the model group. (3) Multiplex immunofluorescence staining and real-time quantitative PCR revealed that compared with the blank control group, protein and gene expression of calcitonin gene-related peptide, tyrosine kinase receptor A, and β3-tubulin were significantly elevated in the femoral head and dorsal root ganglion in the model group. Compared with the model group, protein and gene expression of calcitonin gene-related peptide, tyrosine kinase receptor A, and β3-tubulin were significantly decreased in the femoral head and dorsal root ganglion in both low- and high-dose Gugutou Huaisiyu Capsule groups. (4)The findings suggest that Gugutou Huaisiyu Capsule can elevate the mechanical pain threshold, suppress abnormal neuronal activation, and alleviate pain sensitization in rats with steroid-induced osteonecrosis of the femoral head. This mechanism may involve the inhibition of tyrosine kinase receptor A.

Key words: steroid-induced osteonecrosis of the femoral head, Gugutou Huaisiyu Capsule, tyrosine kinase receptor A, pain sensitization, osteonecrosis, tissue construction

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