关节腔内注射5氟脲嘧啶对兔膝关节炎的疗效评价

Evaluation of intraarticular 5Fu injection in the treatment of rabbit osteoarthritis

目的评价关节腔内注射5氟脲嘧啶(5Fu)对兔膝骨性关节炎的疗效。方法24只兔制成骨关节炎模型动物后随机分成5Fu组、透明质酸(HA)组和对照组3组,5Fu组按2mg/kg关节腔内注射,HA组关节腔内注射HA,对照组注射等量的生理盐水,每周一次连续4次,最后一次治疗后1周处死。观察3组滑膜、软骨组织的光镜改变及MMP-1免疫组化改变,比较关节液、血液中IL-1β的浓度及Mankin's评分。结果5Fu组较之HA组、对照组,软骨病理片显示软骨细胞凋亡减少,软骨基质结构完整、黏多糖含量多;滑膜细胞减少,滑膜下层的纤维增生减轻;血、膝关节滑液IL-1浓度降低(P<0.01),关节软骨中MMP-1表达明显减弱(P<0.01),Mankin's评分有明显改善(P<0.01)。结论关节腔内注射5Fu治疗兔膝关节炎能减轻骨性关节炎的病理过程,保护软骨基质,减轻了滑膜增生,它可能成为治疗骨性关节炎一种新的药物。

Objective To evaluate the effects of intra-articular 5Fu injection in the treatment of rabbit knee osteoarthritis. Methods Twenty-four rabbits were randomly divided into 5Fu group and HA group and control group after the model of OA established. 5Fu group and HA group and control group were received intra-articular 5Fu and HA and physiologic saline injection respectively once a week for 4 weeks and sacrificed one week after the last injection. The histological examinations of cartilage and synovium, immunohistochemistry and morphometric analyses of MMP-1 for cartilage and synovium were delivered. Mankin＇s scale were used for rating. The level of IL-1 β of the serum and synovial fluid were determined by ELISE. Results Compare to HA group and control group, 5Fu group showed reduced apoptosis of chondrocytes and it also kept more integrated structure of matrix and contain more glycosaminoglycan. They could decrease the synoviocytes and inhibit fibrous hyperplasia in synovial underlayer in histological examinations of synovium. The Mankin＇s scale of the group was significantly decreased （P〈0.01）. The level of IL-1 β of the serum and synovial fluid were decreased （P〈0.01 ）. The expression of MMP-1 in the cartilage of 5Fu group decreased （P 〈0.01）. Conclusions Intra-articular 5Fu injection could relieve pathology of OA and protect the matrix of cartilage. It also could decrease the synoviocytes and inhibit fibrous hyperplasia. This procedure could become a new methord to treat osteoarthritis.