三种方法制备兔膝骨关节炎模型的结果分析

Results analysis of the three methods for preparing rabbit knee osteoarthritis model

目的:寻找一种稳定、方便、快捷的膝骨关节炎(Knee Osteoarthritis,KOA)模型制备方法,用以研究KOA的病理机制及防治手段,并为后期科研提供相应理论依据。方法:将24只新西兰大白兔随机分为手术组、制动组、木瓜蛋白酶组、空白组,每组6只。对比模型组(手术组、制动组、木瓜蛋白酶组)家兔造模后与空白组Pelletier评分、Mankin’s评分以及血清及关节液中炎性因子[白细胞介素(Interleukin,IL)-1β、IL-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)-α]的含量水平。结果(:1)大体观察模型组实验兔均出现不同程度的关节僵硬、肿胀,股四头肌萎缩,解剖膝关节均可见股骨内外髁软骨颜色变灰白,软骨面光泽度降低,软骨面有不同程度粗糙、糜烂、溃疡形成,关节周缘骨刺形成;(2)模型组Pelletier评分、Mankin’s评分、血清及关节液中IL-1β、IL-6、TNF-α的含量均高于空白组(P<0.01),模型组与空白组的差异具有统计学意义(P<0.05);(3)关节腔内注射木瓜蛋白酶制备兔KOA模型更方便快捷,短期内效果更佳,木瓜蛋白酶组血清及关节液中IL-1β、IL-6、TNF-α含量高于手术组、制动组(P<0.05),木瓜蛋白酶组与手术组、制动组的差异具有统计学意义(P<0.05);(4)手术、关节制动制备较为复杂并存在较多局限性,如手术感染,重新固定等问题,但可以反映真实状况下KOA的发生发展情况。结论:不同造模方法各有优缺点,现阶段仍未有系统且全面的定论。因此,应根据不同造模方法的优缺点结合后续研究来选择合适的动物疾病模型。

Objective:In order to find a stable,convenient and fast knee osteoarthritis model preparation method to study the pathological mechanism,prevention and treatment of knee osteoarthritis,and provide the corresponding theoretical basis for later research.Methods:Twenty-four New Zealand white rabbits were randomly divided into the surgical group,the brake group,the papain group and the blank group,with 6 rabbits in each group.The levels of Pelletier scores,Mankin’s scores,and inflammatory factors[interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α)]in serum and joint fluid were compared with those in the three groups of rabbits after molding.Results:(1)The experimental rabbits in the model groups showed different degrees of joint stiffness and swelling,quadriceps atrophy,the anatomical knee joint of the condyle cartilage became white and gray,the gloss of the cartilage surface was reduced,the cartilage surface had different degrees of rough,erosion,and the formation of bone spur was found around the peripheral joint.(2)The levels of IL-1β,IL-6,and TNF-αin serum and joint fluid were all higher in the model groups than the blank group(P<0.01),while the comparison between the model group and the blank group was statistically significant(P<0.05).(3)It was easier and faster to prepare rabbit KOA model by intraarticular injection of papain,and the results were better in the short term.The levels of IL-1β,IL-6 and TNF-αin serum and joint fluid in the papain group were higher than those in the operation and the brake group(P<0.05).(4)The preparation of surgery and joint braking was more complex and has many limitations,such as surgical infection,refixation and other problems,but it could reflect the occurrence and development of knee osteoarthritis under the real situation.Conclusion:Different modeling methods have their own advantages and disadvantages,and there is still no systematic and comprehensive conclusion at this stage.Therefore,appropriate animal disease models should be selected according to the advantages and disadvantages of different modeling methods combined with subsequent research.