中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (2): 354-361.doi: 10.12307/2026.546

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

纳米晶胶原基骨联合补肾壮筋汤修复骨质疏松大鼠骨缺损

周世博1，2，俞  兴1，陈海龙2，熊  洋1   

  1. 1北京中医药大学东直门医院骨伤科，北京市  100700；2河南省洛阳正骨医院(河南省骨科医院)脊柱外科，河南省洛阳市  471400
  • 收稿日期:2024-09-12 接受日期:2025-01-06 出版日期:2026-01-18 发布日期:2025-06-16
  • 通讯作者: 俞兴，医学博士，教授，主任医师，博士生导师，北京中医药大学东直门医院骨伤科，北京市 100700 陈海龙，医学硕士，教授，主任医师，硕士生导师，河南省洛阳正骨医院(河南省骨科医院)脊柱外科，河南省洛阳市 471400
  • 作者简介:周世博，男，1994年生，河南省洛阳市人，汉族，医学博士，医师，主要从事中西医结合治疗骨科疾病(骨组织工程，脊柱脊髓损伤，椎间盘退变基础与临床研究)研究。
  • 基金资助:
    国家自然科学基金项目(82305273)，项目负责人：熊洋

Nanocrystalline collagen-based bone combined with Bushen Zhuangjin Decoction repairs bone defects in osteoporotic rats

Zhou Shibo1, 2, Yu Xing1, Chen Hailong2, Xiong Yang1   

  1. 1Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China; 2Department of Spine Surgery, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopaedic Hospital), Luoyang 471400, Henan Province, China
  • Received:2024-09-12 Accepted:2025-01-06 Online:2026-01-18 Published:2025-06-16
  • Contact: Yu Xing, MD, Professor, Chief physician, Docotoral supervisor, Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China Chen Hailong, MS, Professor, Chief physician, Master’s supervisor, Department of Spine Surgery, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopaedic Hospital), Luoyang 471400, Henan Province, China
  • About author:Zhou Shibo, MD, Physician, Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China; Department of Spine Surgery, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopaedic Hospital), Luoyang 471400, Henan Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82305273 (to XY)

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摘要：

文题释义：
纳米晶胶原基骨：是以矿化胶原为基础，采用胶原海绵作为矿化基底，采用自组装方式制备的纳米羟基磷灰石-胶原复合材料，成分和微结构接近天然骨。
骨质疏松骨缺损：骨质疏松是老年男性及绝经后女性常见的代谢性骨病，骨折是骨质疏松常见的并发症之一，骨质疏松骨折后常引发骨折愈合能力减弱、愈合时间延长甚至不愈合，导致骨质疏松骨缺损。

背景：课题组前期研究证实，补肾壮筋汤可以调节骨代谢并发挥抗骨质疏松作用，纳米晶胶原基骨可以辅助四肢骨缺损的修复。 
目的：探索纳米晶胶原基骨联合补肾壮筋汤对骨质疏松骨缺损的修复作用。
方法：将84只雌性SD大鼠随机分为假手术组(n=6，不造模)和双侧卵巢切除组(n=78)，双侧卵巢切除12周后选取假手术组(n=6)、双侧卵巢切除组(n=6)进行骨质疏松造模验证。将双侧卵巢切除组剩余的72只大鼠随机分6组干预，每组12只：A-E组双侧卵巢切除12周后建立股骨缺损(直径3.5 mm，深度4 mm)模型，A组术后给予双蒸水灌胃(1次/d)，B组术后给予补肾壮筋汤灌胃(1次/d)，C组骨缺损部位填充纳米晶胶原基骨后给予双蒸水灌胃(1次/d)，D组骨缺损部位填充纳米晶胶原基骨后给予阿仑膦酸钠灌胃(1次/周)，E组骨缺损部位填充纳米晶胶原基骨后给予补肾壮筋汤灌胃(1次/d)；F组双侧卵巢切除同时建立股骨缺损模型，骨缺损部位填充纳米晶胶原基骨后给予补肾壮筋汤灌胃(1次/d)，均连续给药12周。末次给药12 h后，检测血清Ⅰ型前胶原氨基端原肽、Ⅰ型胶原交联 C-末端肽、雌二醇水平，Micro-CT检测骨缺损区域骨体积，免疫组化染色检测骨缺损区域Ⅰ型胶原及血管内皮生长因子表达。
结果与结论：①与A组相比，D、E组血清Ⅰ型前胶原氨基端原肽水平降低(P < 0.05)；与A、C组相比，D、E、F组血清雌二醇水平升高(P < 0.05)；A-F组缺损区域内骨体积比较差异无显著性意义(P > 0.05)；②免疫组化染色显示，与A组相比，B、D、E组Ⅰ型胶原与血管内皮生长因子表达均增加(P < 0.05)；与C组相比，B、D、E、F组Ⅰ型胶原表达增加(P < 0.05)，D、E、F组血管内皮生长因子表达增加(P < 0.05)；③结果表明，纳米晶胶原基骨联合补肾壮筋汤可能具备修复去卵巢骨质疏松大鼠骨缺损的潜在作用。
https://orcid.org/0000-0003-1260-0807(周世博)；https://orcid.org/0000-0003-3598-3492(俞兴)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 补肾壮筋汤">, 骨质疏松骨缺损">, 纳米晶胶原基骨">, Ⅰ型胶原">, 血管内皮细胞生长因子">, 工程化骨材料

Abstract: BACKGROUND: The previous study of the research group confirmed that Bushen Zhuangjin Decoction can regulate bone metabolism and play an anti-osteoporosis role, and nanocrystalline collagen-based bone can assist in the repair of limb bone defects. 
OBJECTIVE: To explore the repair effect of nanocrystalline collagen-based bone combined with Bushen Zhuangjin Decoction on osteoporotic bone defects. 
METHODS: Totally 84 female SD rats were randomly divided into a sham operation group (n=6, no modeling) and a bilateral ovariectomy group (n=78). After 12 weeks of bilateral ovariectomy, the sham operation group (n=6) and the bilateral ovariectomy group (n=6) were selected for osteoporosis modeling verification. The remaining 72 rats in the bilateral ovariectomy group were randomly divided into 6 intervention groups, with 12 rats in each group: groups A-E had femoral defect models (diameter 3.5 mm, depth 4 mm) established 12 weeks after bilateral ovariectomy. Group A was given double distilled water by gavage (once a day) after surgery; group B was given Bushen Zhuangjin Decoction by gavage (once a day) after surgery; group C had nanocrystalline collagen-based bone filled in the bone defect and then given double distilled water by gavage (once a day); group D had nanocrystalline collagen-based bone filled in the bone defect and then given alendronate sodium by gavage (once a week); group E had nanocrystalline collagen-based bone filled in the bone defect and then given Bushen Zhuangjin Decoction by gavage (once a day); group F had femoral defect models established at the same time after bilateral ovariectomy, and bone defect sites were filled with nanocrystalline collagen-based bone and then given Bushen Zhuangjin Decoction by gavage (once a day). All drugs were given continuously for 12 weeks. 12 hours after the last administration, serum levels of type I procollagen amino-terminal propeptide, type I collagen cross-linked C-terminal peptide, and estradiol were detected; bone volume in the bone defect area was detected by Micro-CT. The expression of type I collagen and vascular endothelial growth factor in the bone defect area was detected by immunohistochemical staining. 
RESULTS AND CONCLUSION: (1) Compared with group A, the serum level of type I procollagen amino-terminal propeptide in groups D and E was decreased (P < 0.05). Compared with groups A and C, the serum estradiol level in groups D, E, and F was increased (P < 0.05). There was no significant difference in the bone volume in the defect area between groups A-F (P > 0.05). (2) Immunohistochemical staining showed that compared with group A, the expression of type I collagen and vascular endothelial growth factor in groups B, D, and E increased (P < 0.05). Compared with group C, the expression of type I collagen in groups B, D, E, and F increased (P < 0.05), and the expression of vascular endothelial growth factor in groups D, E, and F increased (P < 0.05). (3) The results show that nanocrystalline collagen-based bone combined with Bushen Zhuangjin Decoction may have the potential to repair bone defects in ovariectomized osteoporotic rats.

Key words: Bushen Zhuangjin Decoction">, osteoporotic bone defect">, nanocrystalline collagen-based bone">, type I collagen">, vascular endothelial growth factor">, engineered bone material

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