高脂饮食诱导C57BL/6J肥胖小鼠骨关节炎模型的建立

摘要

目的 通过高脂饮食诱导C57BL/6J小鼠肥胖来建立骨关节炎模型并观察其病理特征,为肥胖相关骨关节炎研究中动物模型的建立提供实验依据.方法 C57BL/6J雄鼠20只随机分为对照组和高脂组,分别喂饲基础饲料和高脂饲料.每周测体重及摄食量,16周后收集血清,ELISA法检测血清Ⅱ型胶原C端肽水平;取小鼠左下肢膝关节,固定、脱钙、石蜡包埋,切片后行HE及番红O染色并进行修改后的Mankin评分;TUNEL法检测软骨细胞凋亡.结果 与对照组相比,高脂组小鼠体重、血清Ⅱ型胶原C端肽水平显著升高,而摄食量方面则无明显差异.HE及番红O染色结果显示,高脂组小鼠的膝关节软骨细胞减少,排列混乱,基质染色不均匀,可出现潮线部分缺失,颜色变浅等;且高脂组的修改后的Mankin评分也显著高于对照组.TUNEL检测结果显示,高脂组小鼠关节软骨凋亡细胞数增多,但与对照组相比差异不显著.结论 利用高脂饮食诱导C57BL/6J小鼠肥胖的方法可以建立骨关节炎模型,该模型可用于肥胖相关骨关节炎的研究.%Objective Establish an osteoarthritic model in high-fat diet induced obese mice to study obesity-related osteoarthritis (OA).Methods Twenty C57BL / 6J male mice were randomized into control and high-fat diet groups fed with basic or high-fat diet respectively.Body weight and food intake were measured weekly.Sixteen weeks later serum samples were collected to determine serum collagen typeⅡ C-telopeptide (CTX-Ⅱ) levels by ELISA.Their left knee joints were fixed,decalcified and paraffin embedded for histological examination (HE and Safranin O staining),modified Mankin scoring as well as apoptosis detection (TUNEL assay).Results Compared with control mice,the body weight and serum CTX-Ⅱ level significantly increased in obese mice,while food intake showed no difference.HE and Safranin O staining indicated reduced and disorganized articular chondrocytes,discontinuity of tidemark and poor staining in the knee joints of high-fat diet fed mice.The modified Mankin scores in high-fat diet group were significantly higher than that in control group.TUNEL assay showed that compared to control mice,the number ofapoptotic cells in articular cartilage increased in the high-fat diet fed mice which however was not statistically significant.Conclusion Osteoarthritic model in obese mouse,which may be suitable for obesity related OA study,can be established through feeding mouse with high-fat diet.