口腔医学研究

口腔医学研究 ›› 2026, Vol. 42 ›› Issue (1): 64-69.DOI: 10.13701/j.cnki.kqyxyj.2026.01.012

• 口腔正畸学研究 • 上一篇    下一篇

熊果酸调节Hedgehog信号通路对正畸牙移动模型大鼠骨改建的影响

许诺1*, 韩爽2, 汪世超1, 王莉莉1, 童琳3, 李午丽4   

  1. 1.合肥市口腔医院周谷堆门诊部(安徽医科大学合肥口腔临床学院) 安徽 合肥 240001;
    2.合肥市口腔医院正畸二科 安徽 合肥 240001;
    3.安徽省医学科学研究院 安徽 合肥 230001;
    4.安徽医科大学附属口腔医院牙体牙髓科 安徽 合肥 230011
  • 收稿日期:2025-06-30 出版日期:2026-01-28 发布日期:2026-01-23
  • 通讯作者: *许诺,E-mail:nv1375@sina.com
  • 作者简介:许诺(1982~ ),男,浙江长兴县人,硕士,副主任医师,研究方向:口腔正畸学。
  • 基金资助:
    2024年安徽省卫生健康科研项目(编号:AHWJ2024Aa20222);2023年安徽省卫生健康科研项目(编号:AHWJ2023A20112)

Effect of Ursolic Acid on Bone Remodeling in Orthodontic Tooth Movement Model Rats by Modulating Hedgehog Signaling Pathway

XU Nuo1*, HAN Shuang2, WANG Shichao1, WANG Lili1, TONG Lin3, LI Wuli4   

  1. 1. Department of Zhougudui Outpatient, Hefei Stomatological Hospital (Hefei Clinical College of Stomatology, Anhui Medical University), Hefei 240001, China;
    2. Department 2 of Orthodontics, Hefei Stomatological Hospital, Hefei 240001, China;
    3. Anhui Academy of Medical Sciences, Hefei 230001, China;
    4. Department of Dentistry and Endodontics, Anhui Medical University Affiliated Stomatological Hospital, Hefei 230011, China
  • Received:2025-06-30 Online:2026-01-28 Published:2026-01-23

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摘要： 目的: 探讨熊果酸(ursolic acid,UA)调节Hedgehog信号通路对正畸牙移动模型大鼠骨改建的影响。方法: 构建正畸牙移动大鼠模型,将建模成功的大鼠分为模型组、L-UA、M-UA、H-UA(灌胃15、30、60 mg/kg的UA)、H-UA+Cyclopamine组(灌胃60 mg/kg的UA+腹腔注射15 mg/kg的Hedgehog信号通路抑制剂Cyclopamine),每组各10只。另取10只正常大鼠为Control组,Control组与模型组给予等量生理盐水,1次/d,连续28 d。游标卡尺测量大鼠正畸牙移动距离;HE染色观察大鼠牙周组织骨改建情况;TRAP染色观察大鼠牙周组织破骨细胞;免疫组织化学检测大鼠牙周组织骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)表达强度;Western blot检测大鼠牙周组织中Shh、Ptch-1、Gli-1蛋白表达。结果: 模型组大鼠较Control组组织失去正常上颌骨结构,上颌骨张力侧牙周韧带增宽,牙槽骨改建活跃(P＜0.05);L-UA组、M-UA组、H-UA组大鼠较模型组上颌骨张力侧新骨形成增多,骨吸收陷窝减少且呈剂量依赖性(P＜0.05);H-UA+Cyclopamine组大鼠较H-UA组上颌骨压力侧牙周间隙较窄,可见明显牙骨质表面吸收陷窝(P＜0.05)。模型组大鼠较Control组牙周组织破骨细胞数目、正畸牙移动距离增加,牙周组织BMP-2表达强度升高,Shh、Ptch-1、Gli-1蛋白表达下调(P＜0.05);L-UA组、M-UA组、H-UA组大鼠较模型组牙周组织破骨细胞数目减少,正畸牙移动距离、牙周组织BMP-2表达强度、Shh、Ptch-1、Gli-1蛋白表达升高(P＜0.05);H-UA+Cyclopamine组大鼠较H-UA组牙周组织破骨细胞数目增加,正畸牙移动距离、大鼠牙周组织BMP-2表达强度、Shh、Ptch-1、Gli-1蛋白表达降低(P＜0.05)。结论: UA可通过激活Hedgehog信号通路促进正畸牙移动模型大鼠骨改建。

关键词: 熊果酸, Hedgehog信号通路, 正畸牙移动, 骨改建

Abstract: Objective: To investigate the effect of ursolic acid (UA) on bone remodeling in orthodontic tooth movement model rats by modulating Hedgehog signaling pathway. Methods: A rat model of orthodontic tooth movement was constructed, and the successfully modeled rats were assigned into model group, L-UA, M-UA, H-UA groups (15, 30, 60 mg/kg UA by gavage), and H-UA+Cyclopamine group (60 mg/kg UA by gavage+15 mg/kg Hedgehog signaling pathway inhibitor Cyclopamine by intraperitoneal injection), each with 10 rats. Another 10 normal rats were designated as Control group. The Control group and the model group were given an equal amount of physiological saline once a day for 28 consecutive days. A vernier caliper was used to measure the distance of orthodontic tooth movement in rats. HE staining was used to observe the bone remodeling of periodontal tissue. TRAP staining was used to observe osteoclasts in rat periodontal tissue. Immunohistochemistry was applied to test the expression intensity of bone morphogenetic protein-2 (BMP-2) in periodontal tissue. Western blot was applied to test changes of Shh, Ptch-1, and Gli-1 proteins in rat periodontal tissue. Results: For the Control group, the model group showed loss of normal maxillary structure in rat tissue, widened tension side periodontal ligament, and active alveolar bone remodeling (P<0.05). For the model group, the L-UA group, M-UA group, and H-UA group showed a growth in new bone formation on the tension side of the maxilla in rats, and a gradual reduction in bone resorption cavities in a dose-dependent manner (P<0.05). For the H-UA group, the H-UA+Cyclopamine group had a narrower periodontal gap on the pressure side of the maxilla, with obvious resorption pits on the surface of the dental bone (P<0.05). For the Control group, the model group showed an increase in the number of osteoclasts in the periodontal tissue, an increase in orthodontic tooth movement distance, an increase in BMP-2 intensity in the periodontal tissue, and a downregulation of Shh, Ptch-1, and Gli-1 proteins (P<0.05). For the model group, the L-UA group, M-UA group, and H-UA group showed a decrease in the number of osteoclasts in rat periodontal tissue, a growth in orthodontic tooth movement distance, BMP-2 intensity, Shh, Ptch-1, and Gli-1 proteins in periodontal tissue (P<0.05). For the H-UA group, the H-UA+Cyclopamine group showed a growth in the number of osteoclasts in periodontal tissue, a reduction in orthodontic tooth movement distance, BMP-2 intensity, Shh, Ptch-1, and Gli-1 proteins in periodontal tissue (P<0.05). Conclusion: UA can promote bone remodeling in orthodontic tooth movement model rats by activating the Hedgehog signaling pathway.

Key words: ursolic acid, Hedgehog signaling pathway, orthodontic tooth movement, bone remodeling