[目的]研究口服强力霉素( doxycycline,DOX)和关节腔内注射透明质酸钠(hyaluronic acid,HA)对兔骨关节炎( osteoarthritis,OA)软骨退变的影响及其作用机制.[方法]成年新西兰白兔25只随机分为DOX组、HA组、DOX+HA组、模型组和正常组,每组5只.除正常组外,所有动物均用切断双侧膝关节前、后交叉韧带的方法建立OA模型.术后第9周起,DOX组予DOX 40 mg/(kg·d)灌胃治疗,HA组予HA每周5 mg膝关节腔内注射,DOX+ HA组予DOX 40 mg/(kg·d)灌胃+HA每周5 mg膝关节腔内注射,模型组和正常组不予任何治疗.第17周处死各组动物,对各组膝关节进行大体情况观察,行Pelletier JP评分,并用ELISA法检测关节负重区软骨细胞中β-连环蛋白(β-catenin)表达情况.[结果]模型组关节退变较正常组严重,β-连环蛋白的表达水平较正常组明显升高(P＜0.01).DOX组、HA组和DOX+ HA组三组关节退变较模型组减轻,β-连环蛋白的表达水平也较其明显降低(P ＜0.01)；DOX+ HA组β-连环蛋白表达水平低于DOX组和HA组(P＜0.01),但后两组间β-连环蛋白表达水平差异无显著性意义(P＞0.05).[结论]口服DOX和关节腔内注射HA均可通过抑制β-连环蛋白的生成来阻止OA病变进展,但两药联合使用效果更好.%[Objective] To investigate the effects and mechanism of oral doxycycline ( DOX) and intra - articular injection of hyaluronic acid ( HA ) on experimental osteoarthritis ( OA ) in rabbits. [ Methods ] Twenty - five adult New Zealand white rabbits were randomly divided into 5 groups ( DOX, HA, DOX + HA, model and normal) , and osteoarthritis was induced by severing the anterior and posterior cruciate ligament of the knees in all animals except those in normal group. At 8 week after operation, DOX 40 mg / ( kg ? d) were administered to rabbits of DOX group and DOX + HA group respectively. HA group and DOX + HA group were received intra - articular injection with HA 5 mg per week respectively. Model group and normal group received no treatment. All the animals were sacrificed after 16 weeks, and the gross morphological condition was observed, β - catenin expression in the weight - bearing cartilage of femoral condyles and tibia plateaus weredetected by ELISA. [Results] Compared with the normal group, pathological change was more severe, and β - catenin expression level was significantly higher(P < 0. 01 ) in model group. Pathological changes in DOX group, HA group and DOX + HA group were lighter and (3 - catenin expression level were significantly lower than those in model group ( P < 0.01). The (3 - catenin expression level in DOX + HA group were lower than those in DOX group and HA group (P < 0.01). There were no significant difference in β -catenin expression between DOX group and HA group (P > 0. 05 ). [ Conclusion ] Both of oral DOX and intra - articular injection of HA can inhibit the formation of β - catenin to prevent the progress of OA, and the greater effect could be gotten when they combined.u0000xpressiu0000n betwe
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