颞下颌关节退行性关节病3种小鼠动物模型的构建及病理学特征分析  

Construction and pathological characterization of 3 animal models of temporomandibular joint degenerative joint disease in mice

作　　者：刘欣 江恒华 李慧敏 冯亚平 许利琴 郭慧琳 李颖杰 柯金 龙星 Liu Xin;Jiang Henghua;Li Huimin;Feng Yaping;Xu Liqin;Guo Huilin;Li Yingjie;Ke Jin;Long Xing(The State Key Laboratory Breeding Base of Basic Science of Stomatology&Key Laboratory of Oral Biomedicine Ministry of Education,School of Stomatology,Wuhan University,Wuhan 430079,China)

机构地区：[1]武汉大学口腔医学院口腔基础医学省部共建国家重点实验室培育基地和口腔生物医学教育部重点实验室,武汉430079

出　　处：《中华口腔医学杂志》2022年第10期1057-1064,共8页Chinese Journal of Stomatology

基　　金：国家自然科学基金(82170983)。

摘　　要：目的构建颞下颌关节退行性关节病的3种小鼠动物模型并分析其病理特征,为骨关节炎和骨关节病病理机制的动物实验研究提供参考。方法选取54只8周龄雄性C57BL/6小鼠,分别构建双侧颞下颌关节(temporomandibular joint,TMJ)弗氏完全佐剂(Freund′s complete adjuvant,FCA)注射模型、双侧TMJ碘乙酸钠(monosodium iodoacetate,MIA)注射模型和右侧TMJ关节盘摘除模型3种小鼠颞下颌关节退行性关节病动物模型。FCA注射模型共15只小鼠,分为盐水注射组、FCA-1周组、FCA-2周组、FCA-4周组和FCA-6周组,每组3只小鼠,6侧TMJ。MIA注射模型共15只小鼠,分为盐水注射组、MIA-1周组、MIA-2周组、MIA-4周组和MIA-6周组,每组3只小鼠,6侧TMJ。关节盘摘除模型共24只小鼠,分为对照组、关节盘摘除组-2周、关节盘摘除组-4周和关节盘摘除组-6周,每组6只小鼠(6侧TMJ)。药物注射1 d后,采集小鼠双侧关节区大体照片及关节盘摘除显微手术4周后的髁突组织体视图像。将各时间点小鼠TMJ组织切片分别进行HE染色和甲苯胺蓝染色,并对滑膜组织进行滑膜炎症评分,对髁突软骨组织进行蛋白多糖百分比定量分析。结果FCA或MIA注射1d后,FCA注射组小鼠双侧TMJ宽度[(24.60±0.46)mm]较盐水注射组[(21.63±0.52)mm]显著增加(t=4.25,P=0.013),MIA注射组小鼠双侧TMJ宽度[(24.50±0.62)mm]亦显著大于盐水注射组[(21.40±0.52)mm](t=3.82,P=0.019)。FCA注射组小鼠1、2、4、6周滑膜炎症评分均较盐水注射组显著升高(F=18.09,P<0.001),髁突软骨蛋白多糖百分比较盐水注射组呈现先增多后降低的趋势(F=21.59,P<0.001)。MIA注射组小鼠1、2、4、6周后均出现不同程度的髁突软骨蛋白多糖丢失(F=13.59,P<0.001),滑膜炎症评分较盐水注射组出现不同程度的增加(F=14.79,P<0.001)。髁突体视图像显示关节盘摘除组小鼠髁突软骨形态破坏严重,术后2、4、6周滑膜组织出现结缔组织致密性病变特征,髁突�Objective To explore the pathological characteristics of three mice models of temporomandibular joint degenerative joint disease(TMJDJD),including osteoarthritis and osteoarthrosis,and to provide references for animal experimental study regarding the pathological mechanism of osteoarthritis and osteoarthrosis.Methods A total of 548-week-old male C57BL/6 mice were selected to construct three TMJDJD animal models,including bilateral temporomandibular joint(TMJ)Freund′s complete adjuvant(FCA)injection model,bilateral TMJ monosodium iodoacetate(MIA)injection model,and right TMJ discectomy model.FCA injection model(15 mice)was divided into saline injection group,FCA injection group-1 week,FCA injection group-2 week,FCA injection group-4 week and FCA injection group-6 week,3 mice were used at each time point,with a total of 6 TMJs on both sides.MIA injection model(15 mice)was separated into saline injection group,MIA injection group-1 week,MIA injection group-2 week,MIA injection group-4 week and MIA injection group-6 week,3 mice were used at each time point,with a total of 6 TMJs on both sides.TMJ discectomy model(24 mice)was split into control group,discectomy group-2 week group,discectomy group-4 week and discectomy group-6 week,six mice were used at each time point,with a total of six right TMJs.General pictures of the bilateral joints area of mice were collected 1 day after drug injection,and stereoscopic images of condylar tissues were collected 4 weeks after microsurgery for discectomy.Mouse TMJ tissue sections from each time point were stained with HE and toluidine blue,respectively,synovial tissues were scored for synovial inflammation,and the percentage of proteoglycan in condylar cartilage was quantitatively analyzed.Results One day after intra-articular FCA or MIA injection,the width of bilateral TMJ were significantly increased in FCA injection groups[(24.60±0.46)mm]compared with the saline injection group[(21.63±0.52)mm](t=4.25,P<0.013),the width of bilateral TMJ in MIA injection groups[(24.50±0.62)m

关 键 词：骨关节炎 骨关节病 颞下颌关节退行性关节病 弗氏完全佐剂 碘乙酸钠 关节盘摘除 

分 类 号：R782.6[医药卫生—口腔医学] R-332[医药卫生—临床医学]