早期骨关节炎动物模型的建立与评价

Establishment and evaluation of early knee osteoarthritis model in rabbits

目的建立早期兔膝骨关节炎模型,观察该模型软骨及滑膜的形态学改变,为建立兔膝骨关节炎的早期模型提供依据。方法将20只新西兰大白兔随机分为空白组、模型组。空白组常规饲养,模型组予关节腔注射4%木瓜蛋白酶溶液造模。2周后,观察2组兔膝关节肿胀度,测量膝关节周径及局部皮温,麻醉后取材,膝关节大体观察,取兔膝关节双侧滑膜、股骨髁,常规固定脱钙包埋及切片,对切片分别进行苏木素-伊红(HE)染色、改良番红O-固绿软骨染色及Mankins's评分。结果与空白组比较,模型组软骨HE染色:表层略不平整,无明显裂纹,软骨细胞排列欠规整,偶见软骨细胞簇集;模型组软骨改良番红O-固绿染色:番红染色较淡,阳性范围小;模型组滑膜HE染色:滑膜表层增生明显,有炎性细胞浸润。与空白组相比,模型组Lequesne MG评分和Mankin's评分升高,造模后局部皮温升高,关节宽度增宽。结论予关节腔内注射4%木瓜蛋白酶溶液可以建立早期膝骨关节炎模型,该模型具有周期短、稳定且成功率高的特点,可为建立早期兔膝骨关节炎动物模型提供依据。

Objective To establish a model of early knee osteoarthritis in rabbits and observe the morphological changes of cartilage and synovium in early stage of knee osteoarthritis to provide basis for the establishment of rabbit knee osteoarthritis model. Methods Twenty New Zealand white rabbits were randomly divided into blank control groups and model groups. Except for the blank control groups, the rabbits in the model groups were injected with 4% papain solution in the joint cavity to establish an early knee osteoarthritis model. At the end of the modeling, the swelling degree of the knee joints of two groups of rabbits was observed, and the circumference of the knee joint and the local skin temperature were measured. The total observation of the knee joint was taken by the anesthetized animals. The bilateral femoral condyles of the knee joints of the rabbits were taken, and the conventional fixed decalcification was embedded and sliced. The sections were stained with hematoxylin -eosin (HE), modified red 0-green cartilage and Mankins's. Results Compared with the blank control groups, the model groups of cartilage HE staining showed that the surface was slightly uneven, no obvious cracks, cartilage cells arranged, chondrocytes are irregularly arranged, occasionally chondrocyte clustering. In the model group, the amelioration of the cartilage of the model group was mild and the positive range was small, and the model groups of synovial membrane HE staining: the synovial membrane surface hyperplasia was obvious, and the inflammatory cell infiltration was found in the model group. Compared with the blank control groups, the Lequesne MG score and the Mankin's score in the model group increased, the local skin temperature increased after modeling, and the width of the joint widened after modeling. Conclusion The early knee osteoarthritis model can be established by intra -articular injection of 4% papain solution. The model has the characteristics of short cycle, stable and high success rate, which can provide basis for the establishment of early animal models of rabbit knee osteoarthritis.