延胡索酸对实验性牙周炎小鼠牙槽骨丢失的影响

doi:10.13701/j.cnki.kqyxyj.2025.12.005

摘要/Abstract

摘要： 目的: 以结扎诱导的实验性牙周炎小鼠为模型,探讨延胡索酸(dimethyl fumarate, DMF)对实验性牙周炎小鼠牙槽骨丢失的影响。方法: 分组如下:(1)正常小鼠+溶剂组:正常小鼠,每隔2 d灌胃0.8%羧甲基纤维素(carboxymethyl cellulose, CMC);(2)牙周炎小鼠+溶剂组:小鼠牙周结扎,每隔2 d龈沟注射大肠杆菌脂多糖(lipopolysaccharide, LPS)并灌胃0.8%CMC;(3)牙周炎小鼠+DMF组:小鼠牙周结扎,每隔2 d龈沟注射LPS并灌胃50 mg/kg DMF悬液,均持续2周。实验结束,取3组小鼠左侧上颌骨进行免疫组织化学染色,检测破骨细胞抑制剂骨保护素(osteoprotegerin,OPG)和核因子κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)表达并显微镜观察切片。酶联免疫吸附测定法(enzyme linked immunosorbent assay, ELISA)检测外周血及脾脏白细胞介素-1β(interleukin-1β,IL-1β)表达水平。Micro-CT扫描检测釉牙骨质界至牙槽骨嵴顶(cementoenamel junction to the alveolar bone crest,CEJ-ABC)距离、骨体积分数(bone volume fraction,BV/TV)、骨小梁分离度(trabecular separation,Tb. Sp)和骨小梁厚度(trabecular thickness,Tb. Th),评估牙槽骨丢失情况。苏木精-伊红染色法和抗酒石酸酸性磷酸酶染色,评估组织炎症反应、骨吸收和破骨细胞活性。结果: DMF干预后的牙周炎小鼠CEJ-ABC和Tb. Sp较牙周炎组降低,Tb. Th和BV/TV较牙周炎组增高,外周血及脾脏IL-1β水平较牙周炎组降低,炎症细胞浸润百分比下降,破骨细胞活性及百分比下降。结论: DMF可以减少实验性牙周炎小鼠牙槽骨丢失。

关键词: 延胡索酸, 牙周炎, 白细胞介素-1β, 牙槽骨丢失

Abstract: Objective: To investigate the effect of dimethyl fumarate (DMF) on alveolar bone loss in mice with experimental periodontitis induced by ligation. Methods: The groups were as follows: normal mice + solvent group, normal mice were intragastric administrated with 0.8% carboxymethyl cellulose (CMC) every two days; mice with periodontitis + CMC group, periodontal ligation was performed on the mice, lipopolysaccharide (LPS) was injected into the gingival sulcus every two days, and the mice were intragastrically administered with 0.8% CMC; mice with periodontitis + DMF group, periodontal ligation was carried out on the mice, LPS was injected into the gingival sulcus every two days, and the mice were intragastrically administered with 50 mg/kg DMF suspension. The treatments in the latter two groups were lasted for 2 weeks. At the end of the experiment, the left maxilla of three groups of mice was taken for immunohistochemical staining to detect the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL), and the sections were observed under a microscope. The expression levels of IL-1β in peripheral blood and spleen were detected by ELISA. Micro-CT was used to scan the distance from the cementoenamel junction to the alveolar bone crest (CEJ-ABC), bone volume fraction (BV/TV), trabecular separation (Tb. Sp), and trabecular thickness (Tb. Th) to evaluate alveolar bone loss. Hematoxylin-eosin staining and tartrate-resistant acid phosphatase staining were used to assess tissue inflammatory response, bone resorption, and osteoclast activity. Results: After DMF intervention, the CEJ-ABC and Tb. Sp of periodontitis mice increased and decreased respectively compared with those in the periodontitis group, while the Tb. Th and BV/TV increased compared with the periodontitis group. The level of IL-1β in peripheral blood and spleen were lower than those in the periodontitis group, the percentage of inflammatory cell infiltration decreased, and the activity and percentage of osteoclasts decreased. Conclusion: DMF can reduce alveolar bone loss in mice with experimental periodontitis.

Key words: dimethyl fumarate, periodontitis, IL-1β, loss of alveolar bone

张雨欣, 韦庄, 徐雨瑄, 蔡明, 常志敏, 刘岩. 延胡索酸对实验性牙周炎小鼠牙槽骨丢失的影响[J]. 口腔医学研究, 2025, 41(12): 1044-1049.

ZHANG Yuxin, WEI Zhuang, XU Yuxuan, CAI Ming, CHANG Zhimin, LIU Yan. Effect of Fumaric Acid on Alveolar Bone Loss in Mice with Experimental Periodontitis[J]. Journal of Oral Science Research, 2025, 41(12): 1044-1049.

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