上海交通大学学报(医学版) ›› 2026, Vol. 46 ›› Issue (1): 82-89.doi: 10.3969/j.issn.1674-8115.2026.01.010

• 论著 · 技术与方法 • 上一篇    下一篇

碘乙酸钠诱导大鼠颞下颌关节骨关节炎模型的构建

李梓瑜1, 朱泽宇1, 钱家康1, 陈昱璐1, 陆家瑜2()   

  1. 1.上海交通大学医学院附属第六人民医院口腔科,上海 200233
    2.国家自然科学基金委员会医学科学部,北京 100085
  • 收稿日期:2025-05-05 接受日期:2025-09-22 出版日期:2026-01-28 发布日期:2026-01-30
  • 通讯作者: 陆家瑜,研究员,博士;电子信箱:angelinelu@sjtu.edu.cn
  • 作者简介:第一联系人:李梓瑜、朱泽宇、陆家瑜参与了实验设计,李梓瑜、朱泽宇、钱家康参与了实验操作,朱泽宇负责数据分析,李梓瑜、朱泽宇、钱家康、陈昱璐、陆家瑜参与了论文的写作和修改。所有作者均阅读并同意了最终稿件的提交。
  • 基金资助:
    上海交通大学医学院“双百人”项目(2019-1832)

Construction of a rat model of temporomandibular joint osteoarthritis induced by monosodium iodoacetate

Li Ziyu1, Zhu Zeyu1, Qian Jiakang1, Chen Yulu1, Lu Jiayu2()   

  1. 1.Department of Stomatology, Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
    2.Department of Health Sciences, National Natural Science Foundation of China, Beijing 10085, China
  • Received:2025-05-05 Accepted:2025-09-22 Online:2026-01-28 Published:2026-01-30
  • Contact: Lu Jiayu, E-mail: angelinelu@sjtu.edu.cn.
  • About author:First author contact:The study was designed by Li Ziyu, Zhu Zeyu, and Lu Jiayu. The experiments were completed by Li Ziyu, Zhu Zeyu, and Qian Jiakang. The data were analyzed by Zhu Zeyu. The manuscript was drafted and revised by Li Ziyu, Zhu Zeyu, Qian Jiakang, Chen Yulu, and Lu Jiayu. All authors have read the last version of paper and consented to submission.
  • Supported by:
    “Two-hundred Talents” Program of Shanghai Jiao Tong University School of Medicine(2019-1832)

摘要:

目的·优化关节腔内注射碘乙酸钠(monosodium iodoacetate,MIA)的方法,缩短实验时长,评估构建不同缺损深度大鼠颞下颌关节骨关节炎(temporomandibular joint osteoarthritis,TMJOA)模型的可行性。方法·将18只雄性Sprague-Dawley大鼠随机分为6组。对照组每只双侧关节腔内注射50 μL生理盐水,其余5组按照0.5、1.0、1.5、2.0、2.5 mg/50 μL注射MIA50 μL,分别记为NS组、MIA 1~5组,7 d后取颞下颌关节髁突进行观察分析:采用体视显微镜观察髁突表面形态;使用小动物计算机断层扫描仪(micro computed tomography,micro-CT)扫描并分析大鼠髁突软骨下骨参数[骨体积分数(bone volume/total tissue volume,BV/TV),骨小梁间距(trabecular separation/spacing,Tb.Sp),骨小梁数量(trabecular bone number,Tb.N)];采用苏木精-伊红(hematoxylin-eosin,HE)染色和番红O-固绿染色进行髁突标本的组织学观察,并采用改良Mankin评分法进行评分。结果·与对照组相比,建模7 d后,体视显微镜下见MIA1、MIA2组髁突表面出现微小改变,MIA3、MIA4、MIA5组髁突骨质明显破坏,且破坏分布均匀。Micro-CT三维重建后见MIA3、MIA4、MIA5组髁突骨质明显吸收,MIA1、MIA2组髁突表面局部破坏。骨参数分析后发现MIA4、MIA5组的BV/TV显著降低(P=0.039,P=0.019)、Tb.Sp显著增大(P=0.030,P=0.003),MIA5组Tb.N明显减少(P=0.004)。HE和番红O-固绿染色结果显示:MIA1组纤维层欠光滑,蛋白多糖(红染区)变化不明显;MIA2组结构层次不清,出现无细胞区,蛋白多糖开始减少;MIA3组结构紊乱,细胞数量明显减少;MIA4、MIA5组软骨层几乎不可见。MIA3、MIA4、MIA5组改良Mankin评分均高于对照组(P=0.008,P<0.001,P<0.001)。结论·建模时间为1周时,1.5 mg/50 μL是诱导软骨呈典型TMJOA表现而软骨下骨松质无显著破坏的中间剂量,可用作构建以软骨缺损为主要病变的动物模型,2.0 mg/50 μL MIA可用于建立以软骨下骨破坏为主要特征的大鼠TMJOA模型。

关键词: 颞下颌关节骨关节炎, 碘乙酸钠, 动物模型, 大鼠

Abstract:

Objective ·To optimize the method of injecting monosodium iodoacetate (MIA) into the joint cavity, shorten the experimental duration, and evaluate the feasibility of constructing temporomandibular joint osteoarthritis (TMJOA) models in rats with different degrees of injury. Methods ·Eighteen male Sprague-Dawley rats were randomly divided into 6 groups. The control group was injected with 50 μL of normal saline into the bilateral articular cavities of each rat, and the other 5 groups were injected with MIA at concentrations of 0.5, 1.0, 1.5, 2.0 or 2.5 mg/50 μL. The groups were recorded as the NS group, and MIA 1~5 groups. After 7 days, the condyles of the temporomandibular joint (TMJ) were collected for observation and analysis. The surface morphology of the condyles was observed under a stereomicroscope. Micro-computed tomography (micro-CT) was used to scan and analyze the subchondral bone of the condyles [bone volume/total tissue volume (BV/TV), trabecular separation/spacing (Tb.Sp), and trabecular bone number (Tb.N)]. Hematoxylin-eosin (HE) and safranin O-fast green staining were used for histological observation of the condyle specimens, and the modified Mankin scores were used for evaluation. Results ·Compared with the control group, under a stereomicroscope, minor changes were observed on the condylar surface of the MIA1 and MIA2 groups at 7 days after modeling, while obvious and evenly distributed bone destruction was observed in the condyles of the MIA3, MIA4, and MIA5 groups. Micro-CT three-dimensional reconstruction showed obvious bone resorption in the condyles of the MIA3, MIA4 and MIA5 groups, and local destruction of the condylar surface in the MIA1 and MIA2 groups. Bone parameter analysis revealed a significant decrease in BV/TV (P=0.039, P=0.019) and a significant increase in Tb.Sp in the MIA4 and MIA5 groups (P=0.030, P=0.003); Tb.N was significantly reduced in the MIA5 group (P=0.004). HE and safranin O-fast green staining results showed that the fibrous layer in the MIA1 group was not smooth, and the proteoglycan content (red-stained area) did not change significantly. The structure of the MIA2 group was unclear, cell-free areas appeared, and proteoglycan began to decrease. The structure of the MIA3 group was disordered and the number of cells was significantly reduced. The cartilage layer in the MIA4 and MIA5 groups was almost invisible. The modified Mankin scores in the MIA3, MIA4 and MIA5 groups were higher than those in the control group (P=0.008, P<0.001, P<0.001). Conclusion ·When the modeling time is 1 week, 1.5 mg/50 μL is an intermediate dose that induces typical TMJOA manifestations in cartilage without significant destruction of subchondral bone, and can be used to construct an animal model with cartilage defects as the main lesion.A dose of 2.0 mg/50 μL MIA can be used to establish a rat TMJOA model with subchondral bone destruction as the main feature.

Key words: temporomandibular joint osteoarthritis (TMJOA), monosodium iodoacetate (MIA), animal model, rat

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