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

关键词:  骨关节炎  强力霉素  透明质酸钠  β-连环蛋白  软骨退变

Key words:  osteoarthritis  doxycycline  hyaluronic acid  β-catenin  cartilage degeneration

摘要:

[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。

Abstract:

[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(P<0.01) 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 (P<0.01). The β-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.