强力霉素与透明质酸钠对兔骨关节炎的影响及其作用机制的研究

Effects of doxycycline and hyaluronate acid on osteoarthritis of rabbits

[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 were detected by ELISA.[Results]Compared with the normal group,pathological change was more severe,and β-catenin expression level was significantly higher（P0.01） in model group.Pathological changes in DOX group,HA group and DOX＋HA group were lighter and β-catenin expression level were significantly lower than those in model group（P0.01）.The β-catenin expression level in DOX ＋ HA group were lower than those in DOX group and HA group（P0.01）.There were no significant difference in β-catenin expression between DOX group and HA group（P0.05）.[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.