中国组织工程研究

中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (12): 1927-1930.doi: 10.12307/2022.518

• 骨科植入物相关基础实验 Basic experiments of orthopedic implant • 上一篇    下一篇

丹酚酸B干预去卵巢骨质疏松模型大鼠的生物学变化及机制

王  东，丁  海，常文举，王金子   

  1. 蚌埠医学院第一附属医院骨科，安徽省组织移植实验室，安徽省蚌埠市   233000
  • 收稿日期:2021-07-06 修回日期:2021-07-08 接受日期:2021-08-12 出版日期:2022-04-28 发布日期:2021-12-15
  • 通讯作者: 丁海，博士，主任医师， 蚌埠医学院第一附属医院骨科，安徽省组织移植实验室，安徽省蚌埠市 233000
  • 作者简介:王东，男，1994年生，安徽省怀远县人，汉族，蚌埠医学院在读硕士，医师，主要从事骨质疏松相关研究。
  • 基金资助:
    蚌埠医学院自然科学重点项目(2020byzd096)，项目负责人：常文举

Biological changes and mechanism of salvianolic acid B in ovariectomized osteoporosis rat models

Wang Dong, Ding Hai, Chang Wenju, Wang Jinzi   

  1. Department of Orthopedics, First Affiliated Hospital of Bengbu Medical College, Anhui Tissue Transplantation Laboratory, Bengbu 233000, Anhui Province, China
  • Received:2021-07-06 Revised:2021-07-08 Accepted:2021-08-12 Online:2022-04-28 Published:2021-12-15
  • Contact: Ding Hai, MD, Chief physician, Department of Orthopedics, First Affiliated Hospital of Bengbu Medical College, Anhui Tissue Transplantation Laboratory, Bengbu 233000, Anhui Province, China
  • About author:Wang Dong, Master candidate, Physician, Department of Orthopedics, First Affiliated Hospital of Bengbu Medical College, Anhui Tissue Transplantation Laboratory, Bengbu 233000, Anhui Province, China
  • Supported by:
    Natural Science Key Project of Bengbu Medical College, No. 2020byzd096 (to CWJ)

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摘要：

文题释义：
核因子κB受体活化因子配体(receptor activator of nuclear factor kappa B ligand，RANKL)：活化的T细胞、树突状细胞释放RANKL，RANKL属于肿瘤坏死因子及其受体超家族。RANK表达于破骨细胞及其前体细胞表面的Ⅰ型跨膜蛋白。二者相互结合形成三聚体，其结合信号经信号通路逐步下传，最终激活相关靶基因，促进破骨细胞分化成熟。
丹酚酸B(Salvianolic acid B)：是中药丹参的生物活性成分，药理作用广泛，具有抗炎、抗氧化、抗肿瘤、保护中枢神经系统、改善微循环、防止血栓形成及改善心肌缺血等多种作用。最近的研究发现，丹参具有雌激素样作用，能够调节钙磷代谢和碱性磷酸酶水平，修复骨组织损伤。

背景：丹酚酸B抗骨质疏松的机制不同于传统抗骨吸收药物，呈多靶点的药理效应，目前尚未完全阐明。
目的：研究丹酚酸B对骨质疏松大鼠股骨与腰椎骨密度的影响，探讨其抗骨质疏松的作用机制。
方法：6月龄SPF级SD大鼠36只，随机分成3组：假手术组、骨质疏松组、丹酚酸B组。骨质疏松组和丹酚酸B组行大鼠双侧卵巢摘除术，复制骨质疏松症模型；假手术组保留完整卵巢，取出部分脂肪组织。术后4周，丹酚酸B组给予50%丹酚酸B 25 mg/kg，每周灌胃给药6 d，持续12周，其余2组给予等量生理盐水，时间相同。术后16周，麻醉后处死全部大鼠，采用双能X射线吸收仪扫描大鼠右后股骨和腰椎骨密度，酶联免疫吸附法检测血清骨保护素、核因子κB受体活化因子配体水平。实验方案经蚌埠医学院动物管理委员会审批，批号：[2021]第255号。
结果与结论：①骨质疏松组大鼠股骨骨密度比假手术组低(P < 0.05)，丹酚酸B组大鼠股骨骨密度比骨质疏松组高，但差异无显著性意义(P > 0.05)；骨质疏松组大鼠腰椎骨密度较假手术组差异无显著性意义(P > 0.05)，丹酚酸B组腰椎骨密度较骨质疏松组增高，但差异无显著性意义(P > 0.05)；②骨质疏松组大鼠血清骨保护素水平明显低于假手术组(P < 0.05)，丹酚酸B组大鼠血清骨保护素水平比骨质疏松组高，但差异无显著性意义(P > 0.05)；骨质疏松组大鼠血清核因子κB受体活化因子配体水平明显高于假手术组(P < 0.05)，丹酚酸B组大鼠血清核因子κB受体活化因子配体比骨质疏松组低，但差异无显著性意义(P > 0.05)；③结果说明，绝经后骨质疏松症早期大鼠股骨骨密度减少较为显著，腰椎骨密度无显著变化；目前尚不能认为短期单独应用丹酚酸B可以有效治疗骨质疏松症。
缩略语：核因子κB受体活化因子配体：receptor activator of nuclear factor kappa B ligand，RANKL；核因子κB受体活化因子：receptor activator of nuclear factor kappa B，RANK；骨保护素：osteoprotegerin，OPG

https://orcid.org/0000-0002-2277-9460 (王东) 

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

关键词: 大鼠, 丹酚酸B, 骨质疏松, 骨保护素, RANKL

Abstract: BACKGROUND: The anti-osteoporotic mechanism of salvianolic acid B is different from traditional anti-bone resorption drugs. It has a multi-target pharmacological effect, which has not yet been fully elucidated.  
OBJECTIVE: To study the effect of salvianolic acid B on bone density of femur and lumbar vertebra in rats with osteoporosis, and to explore its anti-osteoporotic mechanism.
METHODS:  Totally 36 SPF SD rats aged 6 months were randomly divided into three groups: sham operation group, osteoporosis group, and salvianolic acid B group. Bilateral ovaries were removed and the osteoporosis model was replicated in the osteoporosis group and salvianolic acid B group. In the sham operation group, intact ovaries were kept and part of adipose tissue was removed. At 4 weeks after surgery, 50% salvianolic acid B 25 mg/kg was given by gavage for 6 days per week for 12 consecutive weeks in the salvianolic acid B group. In the other two groups, the same amount of normal saline was given for the same time. At 16 weeks postoperatively, all the rats were sacrificed after anesthesia. The bone density of the right posterior femur and lumbar vertebra was scanned by dual-energy X-ray absorptiometry. The levels of osteoprotegerin and receptor activator of nuclear factor-kB ligand in serum were detected by enzyme-linked immunosorbent assay. The protocols were approved by the Animal Management Committee of Bengbu Medical College (approval No. [2021]255).  
RESULTS AND CONCLUSION: (1) The bone mineral density of femur in the osteoporosis group was lower than that in the sham group (P < 0.05). The femoral bone mineral density of salvianolic acid B group was significantly higher than that of osteoporosis group (P > 0.05). The bone mineral density of lumbar vertebrae in osteoporosis group was not significantly different from that in sham operation group (P > 0.05). The lumbar vertebrae bone density of salvianic acid B group was higher than that of osteoporosis group, but the difference was not significant (P > 0.05). (2) Osteoprotegerin level of osteoporosis group was lower than that of sham operation group (P < 0.05). Osteoprotegerin level of salvianolic acid B group was higher than that of osteoporosis group, but the difference was not significant (P > 0.05). The level of receptor activator of nuclear factor-kB ligand of osteoporosis group was significantly higher than that of sham operation group (P < 0.05). The level of receptor activator of nuclear factor-kB ligand of salvianolic acid B group was lower than that of osteoporosis group, but the difference was not significant (P > 0.05). (3) These findings suggest that in the early stage of postmenopausal osteoporosis, bone mineral density of femur decreased significantly, but there was no significant change in bone mineral density of the lumbar spine. At present, it is not believed that salvianolic acid B alone can effectively treat osteoporosis in the short term.

Key words: rats, salvianolic acid B, osteoporosis, osteoprotegerin, receptor activator of nuclear factor-kB ligand

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