早期膝骨性关节炎模型大鼠的建立与验证  

Establishment and verification of rat models of early knee osteoarthritis

作　　者：何强 尹宏[2] 代凤雷 张斌[3] 孙欣[2] 曾怿[3] 严一峰 He Qiang;Yin Hong;Dai Fenglei;Zhang Bin;Sun Xin;Zeng Yi;Yan Yifeng(Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China;Department of Orthopedics, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China;Department of Orthopedics, Liuhe Hospital Affiliated to Yangzhou University Medical College, Nanjing 211500, Jiangsu Province, China)

机构地区：[1]南京中医药大学,江苏省南京市210023 [2]南京中医药大学附属南京中医院骨科,江苏省南京市210001 [3]扬州大学医学院附属六合医院骨科,江苏省南京市211500

出　　处：《中国组织工程研究》2019年第27期4338-4343,共6页Chinese Journal of Tissue Engineering Research

基　　金：南京市医学科技发展一般性课题(YKK17240),项目负责人:张斌~~

摘　　要：背景:木瓜蛋白酶诱导膝关节骨性关节炎与其他化学诱导试剂相比优势在于对胶原蛋白和软骨细胞没有直接影响。目的:通过软骨的表面形态、放射学和组织病理学进一步验证木瓜蛋白酶诱导大鼠早期膝关节骨性关节炎模型的有效性。方法:20只成年雄性Wistar大鼠,由南京市江宁区青龙山动物繁殖场提供,实验方案经南京市六合区人民医院医学伦理委员会批准。将大鼠随机分成对照组和实验组:分别于实验开始后第1,4,7天,给予对照组右膝关节腔内注射4%生理盐水;实验组右膝关节腔内注射4%木瓜蛋白酶。实验开始后第10天观察关节软骨形态,行X射线、三维CT检查;之后麻醉下处死大鼠即刻进行组织病理学检查,并使用Mankins和OARSI评分验证结果。结果与结论:①与对照组相比,实验组大鼠明显跛行,注射侧膝关节肿胀明显,后肢不愿着地;放射学检查可见明显关节间隙变窄,三维CT关节间隙值变小[对照组(0.680 0±0.016 3) mm,实验组(0.558 0±0.033 9) mm,P<0.05];②实验组右膝关节组织显微镜下观察可见早期的炎症特征;2组病理学Mankins和OARSI评分差异均有显著性意义(P <0.05);③结果说明,大鼠右膝关节腔内注射木瓜蛋白酶诱发的早期膝骨性关节炎可用于相关实验研究,因为它提供了关节运动、触觉异常性疼痛、进行性放射性变性和关节软骨微观炎症的可测量变化,代表了骨关节炎评估,为研究早期膝关节骨性关节炎的发病机制提供依据。BACKGROUND: Papain inducing knee osteoarthritis has no direct effect on collagen and chondrocyte compared with other chemical inducers.OBJECTIVE: To evaluate the effectiveness of early osteoarthritis model of knee joint in rats by the surface morphology, radiology and histopathology of cartilage.METHODS: Twenty adult male Wistar rats were provided by Qinglongshan Animal Breeding Farm of Jiangning District, Nanjing, and the study was approved by the Ethics Committee of Liuhe Hospital Affiliated to Yangzhou University Medical College. The rats were randomly divided into control and experimental groups. At 1, 4 and 7 days, 4% normal saline and 4% papain were injected into the rat right knee joint cavity in the control and experimental groups, respectively. Rats were killed at 10 days. The articular cartilage morphology,X-ray and three-dimensional CT images were observed before the execution. Histopathological examination was performed immediately after the execution, and the results were verified by Mankins and OARSI scores.RESULTS AND CONCLUSION:(1) Compared with the control group, in the experimental group, the limp was obvious, the knee joint swelling on the injection side was obvious, and the hind limbs were unwilling to land. Radiological examination showed that the joint space narrowed obviously, and the value of three-dimensional CT joint space was significantly decreased [(0.680 0±0.016 3)vs.(0.558 0±0.033 9) mm, P < 0.05].(2) Microscopic examination showed early stage inflammation characteristics at the right knee joint in the experimental group. There were significant differences in the Mankins and OARSI scores(P < 0.05).(3) In summary, early knee osteoarthritis induced by intra-articular injection of papain into the right knee joint of rats can be used in relevant clinical studies, because it provides measurable changes in joint motion, tactile abnormal pain, progressive radiodegeneration and micro-inflammation of articular cartilage, representing the evaluation of osteoarthritis, and providing a basis

关 键 词：大鼠模型 早期膝骨性关节炎 关节软骨 木瓜蛋白酶 

分 类 号：R446[医药卫生—诊断学] R318[医药卫生—临床医学]