小白菊内酯不同给药途径对兔膝骨关节炎的实验研究

摘要

Objective By measuring the levels of TNF⁃α and IL⁃1β in serum and synovial fluid in rabbit model of knee osteoarthritis ( OA) , to observe the histological changes of the cartilage and to explore the efficacy and mechanism of parthenolide on osteoarthritis with different administration routes. Methods Forty healthy purebred New Zealand rabbits were randomly divided into control group (group A, n=8), and OA model groups established using plaster cast immobilization of the right hind limb extension (n=32). After modeling the rabbits were randomly divided into 4 groups, the model of oral control group (group B), model of intra⁃articular injection control group (group C), parthenolide oral group (group D), parthenolide articular injection group (group E) , with 8 rabbits in each group. After 6⁃week treatment, the expression levels of TNF⁃αand IL⁃1βin the serum and knee fluid were measured. All animals were sacrificed at 8 weeks, the histopathological changes in articular cartilage were observed using hematoxylin⁃eosin ( HE) staining. Results TNF⁃α and IL⁃1β concentrations in synovial fluid and serum were significantly lower in rabbits of group D and E than those in group B and C ( P<0�05 ) , and the decrease was more significant in group E than in group D ( P<0�05). Comparing with those in group A, the relevant sections in group B and C showed pathological cartilage damage, and the pathological scores increased (P<0�05). Comparing with those in group D and E, the pathological changes in group B and C showed some repair in articular cartilage, and the pathological scores decreased (P<0�05). Conclusion Parthenolide relieves arthritis in the animal model. The anti⁃inflammatory effect of intra⁃articular administration is better than oral administration. It inhibits secretion of serum and articular TNF⁃αand IL⁃1β, which may be one of the mechanisms of parthenolide in the treatment of arthritis.%目的：通过测定膝骨关节炎兔模型血清和关节液中TNF⁃α、IL⁃1β的含量，观察软骨的组织学改变，探讨小白菊内酯不同给药途径治疗骨关节炎的疗效与作用机制。方法健康纯种新西兰兔40只，随机取8只作为正常组（ A组）；其余的32只采用右后肢伸直位管型石膏固定法，建立OA模型。造模后随机分为4组：模型口服对照组（ B组）、模型关节腔注射对照组（C）、小白菊内酯口服组（D组）、小白菊内酯关节腔注射组（E组），每组8只。 B组和D组兔分别予生理盐水、小白菊内酯灌胃，C组和E组兔分别予生理盐水、小白菊内酯关节腔注射，连续治疗6w后，测定各组兔治疗前后血清、膝关节液TNF⁃α、IL⁃1β表达水平。所有实验动物在8w处死，应用苏木素⁃伊红（HE）染色观察各组动物关节软骨的病理组织改变。结果与模型组（ B组、C组）比较，D组、E组关节液及血清中的TNF⁃α、IL⁃1β浓度均明显降低（ P＜0�05），且E组降低幅度明显大于D组（P＜0�05）。与A组比较，B组和C组病理显示有关节软骨破坏，病理积分升高（P＜0�05）；D组、E组病理改变较B组、C组显示关节软骨有所修复，病理积分降低（P＜0�05）。结论小白菊内酯可减轻动物模型的关节炎症，其关节腔给药的抗炎疗效优于口服给药，抑制血清和关节腔TNF⁃α、IL⁃1β的分泌，可能是小白菊内酯治疗骨关节炎的机制之一。