中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (28): 7280-7286.doi: 10.12307/2026.400

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

构建早期膝骨关节炎大鼠模型:CatWalk步态分析评估

摆  雪1,2,田育魁1,2,郭  蕾1,2,石梦妮3,崔小锋1,2,王  程1,李静先4,朱清广3,刘俊昌1,2   

  1. 1新疆医科大学中医学院,新疆维吾尔自治区乌鲁木齐市   830017;2新疆医科大学第四附属医院,新疆维吾尔自治区乌鲁木齐市   830000;3上海中医药大学附属岳阳中西医结合医院,上海市   200437;4加拿大渥太华大学健康科学学院,渥太华   K1N 6N5
  • 收稿日期:2025-06-30 修回日期:2025-11-15 出版日期:2026-10-08 发布日期:2026-02-10
  • 通讯作者: 刘俊昌,硕士,主任医师,教授,博士生导师,新疆医科大学中医学院,新疆维吾尔自治区乌鲁木齐市 830017;新疆医科大学第四附属医院,新疆维吾尔自治区乌鲁木齐市 830000
  • 作者简介:摆雪,女,1989年生,宁夏回族自治区隆德县人,回族,新疆医科大学在读博士,主治医师,讲师,主要从事中西医结合治疗骨关节疾病的研究。
  • 基金资助:
    国家自然科学基金项目(82360979),项目负责人:刘俊昌;新疆维吾尔自治区科技创新团队(天山英才团队)项目(2022TSYCTD0008),项目负责人:刘俊昌

Construction of an early knee osteoarthritis rat model: CatWalk-based gait analysis and evaluation

Bai Xue1, 2, Tian Yukui1, 2, Guo Lei1, 2, Shi Mengni3, Cui Xiaofeng1, 2, Wang Cheng1, Li Jingxian4, Zhu Qingguang3, Liu Junchang1, 2   

  1. 1College of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi 830017, Xinjiang Uygur Autonomous Region, China; 2The Fourth Affiliated Hospital, Xinjiang Medical University, Urumqi 830000, Xinjiang Uygur Autonomous Region, China; 3Yueyang Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; 4Faculty of Health Sciences, University of Ottawa, Ottawa K1N 6N5, Canada
  • Received:2025-06-30 Revised:2025-11-15 Online:2026-10-08 Published:2026-02-10
  • Contact: Liu Junchang, MS, Chief physician, Professor, Doctoral supervisor, College of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi 830017, Xinjiang Uygur Autonomous Region, China; The Fourth Affiliated Hospital, Xinjiang Medical University, Urumqi 830000, Xinjiang Uygur Autonomous Region, China
  • About author:Bai Xue, PhD candidate, Attending physician, Lecturer, College of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi 830017, Xinjiang Uygur Autonomous Region, China; The Fourth Affiliated Hospital, Xinjiang Medical University, Urumqi 830000, Xinjiang Uygur Autonomous Region, China
  • Supported by:
    the National Natural Science Foundation of China, No. 82360979 (to LJC); the Xinjiang Uygur Autonomous Region Scientific and Technological Innovation Team Program (Tianshan Talent Team Project), No. 2022TSYCTD0008 (to LJC)

摘要:



文题释义:
寒湿痹阻:寒湿痹阻证是指由于寒邪与湿邪相结合,侵袭人体经络、肌肉、关节,导致气血运行不畅,经络痹阻不通,从而出现以肢体关节冷痛、重着、屈伸不利为主要临床表现的一种证候,它是痹证中最常见的基本证型之一。
早期膝骨关节炎:特指疾病进程的初始阶段,此时病理改变尚属轻微,具有可逆性干预窗口期,临床主要表现为间断性、轻度膝关节症状,影像学尚未达到典型骨关节炎诊断标准(如Kellgren-Lawrence分级为0-1级)。

背景:现有膝骨关节炎动物模型多关注机械损伤因素,缺乏对中医“寒湿痹阻”证候特征的模拟及观测。
目的:构建中西医病因结合的寒湿痹阻型膝骨关节炎模型,并通过多维度评价体系验证其有效性。
方法:24只SPF级SD雄性大鼠随机分为假手术组、模型组、寒湿痹阻组。后两组大鼠均行右后肢膝关节前交叉韧带断裂术,寒湿痹阻组大鼠术后14 d接受人工寒湿环境干预(温度10.5 ℃,湿度90%,4 h/d,持续4周),假手术组大鼠剪开皮肤暴露膝关节后即刻缝合。分别在造模前、造模后1,2周及寒湿痹阻干预后4周,对各组大鼠进行中医证候评分、CatWalk步态分析,取右后肢膝关节组织进行病理学观察和Mankin评分。
结果与结论:①中医证候评分:寒湿痹阻组大鼠在后期出现明显的精神萎靡、少动、便溏、舌质紫黯、皮毛无光泽等症状,摄食量减少,体质量增长缓慢(P < 0.01)。②CatWalk步态参数:造模后1周与假手术组比较,模型组和寒湿痹阻组大鼠右后肢最大接触强度下降、脚印长度减小、最大强度减小、右后肢15个最大像素的平均强度减小、右后肢摆动时相增加(均P < 0.01),寒湿痹阻组大鼠右后肢摆动速度显著下降(均P < 0.05);放入人工气候箱4周后与假手术组比较,寒湿痹阻组大鼠右后肢最大接触强度、最大强度、右后肢15个最大像素的平均强度显著下降(P < 0.01),右后肢摆动时相显著增加(P < 0.01),摆动速度明显下降(P < 0.05)。③病理学观察:模型组和寒湿痹阻组组织Mankin评分较假手术组均显著提高(P < 0.01),寒湿痹阻组Mankin评分显著高于模型组(P < 0.01)。结果说明,前交叉韧带切断术联合寒湿环境可成功构建寒湿痹阻型早期膝骨关节炎大鼠模型,CatWalk步态参数与中医证候评分变化为膝骨关节炎的中医药机制研究提供客观评价体系。
https://orcid.org/0009-0003-7655-080X (摆雪)


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: 膝骨关节炎, 寒湿痹阻证, 前交叉韧带断裂, CatWalk步态分析

Abstract: ACKGROUND: Studies on existing animal models of knee osteoarthritis predominantly focus on mechanical injury factors but fail to simulate and observe the “cold-dampness obstruction” syndrome characteristics in traditional Chinese medicine. 
OBJECTIVE: To construct a traditional Chinese medicine-Western medicine integrated knee osteoarthritis model for cold-dampness obstruction syndrome and validate its efficacy via a multidimensional assessment. 
METHODS: Twenty-four male Sprague-Dawley rats (SPF-grade) were randomly divided into sham surgery, model, and cold-dampness obstruction groups. Both the model and cold-dampness obstruction groups underwent anterior cruciate ligament transection. The cold-dampness obstruction group was exposed to an artificial cold-dampness environment (10.5°C, 90% humidity, 4 h/d, for 4 weeks) starting from 14 days post-surgery. At baseline, 1 and 2 weeks after modeling, and 4 weeks after cold-dampness obstruction intervention, all groups underwent following assessments: traditional Chinese medicine syndrome scoring, automated gait analysis using the CatWalk system, and histological examination with Mankin scoring of the right hindlimb knee joint.
RESULTS AND CONCLUSION: (1) Traditional Chinese medicine syndrome scoring: The cold-dampness obstruction group exhibited significant lethargy, hypoactivity, diarrhea, cyanotic tongue coloration, dull fur coat, decreased food intake, and attenuated weight gain (P < 0.01). (2) CatWalk gait parameters: One week after modeling, the model and cold-dampness obstruction groups showed significant differences compared with the sham surgery group in terms of hindlimb maximum contact intensity, hindlimb footprint length, hindlimb peak intensity, hindlimb average intensity of 15 maximum pixels, and hindlimb swing phase (all P < 0.01). The cold-dampness obstruction group showed significantly reduced hindlimb swing speed (all P < 0.05). After 4 weeks of cold-dampness intervention, the cold-dampness obstruction group displayed significant reductions in hindlimb maximum contact intensity, peak intensity, and average intensity of 15 maximum pixels compared with the sham surgery group (P < 0.01), along with prolonged hindlimb swing phase (P < 0.01) and decreased swing speed (P < 0.05). (3) Histopathology: Mankin scores significantly increased in the model and cold-dampness obstruction groups compared with the sham surgery group (P < 0.01), while the score in the cold-dampness obstruction group was higher than that in the model group (P < 0.01). These findings indicate that anterior cruciate ligament transection combined with cold-dampness environment can successfully establish a rat model of early knee osteoarthritis with cold-dampness obstruction syndrome. Quantitative gait analysis using the CatWalk system, combined with standardized traditional Chinese medicine syndrome scoring, provides an objective evaluation framework for investigating the mechanisms of traditional Chinese medicine-based osteoarthritis models.

Key words: knee osteoarthritis, cold-dampness obstruction syndrome, anterior cruciate ligament transection, CatWalk gait analysis

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