中国骨质疏松杂志

绝经后股四头肌肌肉萎缩膝骨关节炎大鼠模型的建立及鉴定

Establishment and identification of postmenopausal knee osteoarthritis rat model with quadriceps femoris muscle atrophy

DOI：10.3969/j.issn.1006-7108.2023.08.001

中文关键词: 膝骨关节炎肌肉萎缩股四头肌肉毒素A 大鼠

英文关键词:knee osteoarthritis muscle atrophy quadriceps femoris botulinum toxin A rat

基金项目:广东省基础与应用基础研究基金项目（2021A1515011545）；广东省科技计划项目（2021B11111610007；2019A141401008）；广州市科技计划项目（202002030204）

作者	单位
陈泽华1 申震2 陈国茜3 许学猛1,4* 刘文刚1,4*	1. 株洲市中医伤科医院，湖南株洲 412000 2. 昆明市中医院/云南中医药大学第三附属医院，云南昆明 650011 3. 浙江省中医院骨伤科，浙江杭州 310000 4. 广东省第二中医院，广东广州 510405

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中文摘要:

目的建立一种稳定的绝经后股四头肌肌肉萎缩膝骨关节炎（knee osteoarthritis，KOA）大鼠模型。方法将40只雌性SD大鼠随机分为卵巢切除组（OVX组）、卵巢切除+肉毒素组（OVX+BTX组）、肉毒素组（BTX组）和空白组（Control组），于造模后4周、9周分别对各组大鼠进行抓力测定和Lequesne MG评分，对股四头肌、滑膜和膝关节进行切片染色，进行关节软骨Mankin评分和滑膜炎症评分。结果造模后第4、9周OVX+BTX组和BTX组股四头肌肌肉萎缩明显；造模后第4周OVX+BTX组和BTX组大鼠Lequesne MG评分均明显高于Control组（均P < 0.05），第9周时OVX+BTX组和BTX组大鼠Lequesne MG评分均大于Control组（均P < 0.01）；造模第4周和第9周OVX+BTX组的四肢抓力体重比和双后肢抓力体重比均明显低于Control组（均P < 0.05），且造模第9周时OVX+BTX组和BTX组的双后肢抓力和抓力体重比均明显低于Control组（均P< 0.05）；造模第4周时，OVX+BTX组和BTX组的Mankin评分均明显高于Control组（均P < 0.05）；造模第9周时，OVX+BTX组、OVX组、BTX组的Mankin评分均明显大于Control组（均P < 0.05）。造模第4周各组滑膜炎症均不明显，第9周时OVX组、OVX+BTX组和BTX组的滑膜炎性评分均明显大于Control组（均P < 0.01）。结论本研究中所涉及的三种造模方法均可建立KOA模型，而肉毒素股四头肌肌注结合卵巢切除建立的KOA模型，关节软骨破坏更明显，且更符合绝经后KOA肌肉和骨骼的真实病理变化，有利于进一步研究KOA发病及防治过程中肌肉和骨骼之间的关系。

英文摘要:

Objective To establish a stable knee osteoarthritis(KOA) rat model of quadriceps femoris muscle atrophy. Methods Forty female SD rats were randomly divided into ovariectomized group (OVX), ovariectomized + botulinum toxin group (OVX + BTX), botulinum toxin group (BTX) and control group (Control). Five rats were selected from each group at 4W and 9W after modeling. The grip strength and Lequesne MG score in each group were evaluated, and the sections of quadriceps femoris, synovium and knee joint were stained, Mankin score of articular cartilage and synovitis score were performed. Results At the 4th and 9th week after modeling, quadriceps muscle atrophy occurred significantly in OVX + BTX group and BTX group. At the 4th week after modeling, the Lequesne MG scores of OVX + BTX group and BTX group were significantly higher than those of OVX group and Control group (all P<0.05). At the 9th week, the Lequesne MG scores of OVX + BTX group, BTX group and OVX group were higher than those of Control group, all P< 0.01. Moreover, the four-limb grip weight ratio and two lower limb grip weight ratio of OVX + BTX group were significantly lower than those of Control group at the 4th and 9th week after modeling (all P<0.05), and the two lower limb grip strength and strength weight ratio of OVX + BTX group and BTX group were significantly lower than those of Control group at the 9th week after modeling (all P<0.05). At the 4th week after modeling, Mankin scores in the OVX + BTX group and BTX group were and, significantly higher than that in control group (P<0.05), but compared with OVX group had no statistical difference (P<0.05). At the 9th week after modeling, the Mankin score of OVX + BTX group was significantly higher than that in OVX group, BTX group and control group, all the differences were statistically significant (P<0.05). Furthermore, synovitis was not obvious in each group at the 4th week, whilesynovitis was observed in the three model groups at the 9th week. The synovitis scores of the three model groups were significantly higher than those of the control group (P<0.01). The synovitis scores of the three model groups were significantly higher than those of the Control group (all P<0.01). Conclusion KOA model can be established by the three methods, and articular cartilage damage is more distinct in the KOA model established by botulinum toxin injection combined with ovariectomy, which is more comparable to the real pathological changes of muscle and bone in postmenopausal KOA.

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