阿伦膦酸钠防治人工关节松动的实验研究

Experiment study of alendronate in the prevention and treatment of aseptic loosening of prosthesis

目的:评价二膦酸盐阿伦膦酸钠在防治人工关节松动中的作用。方法:36只SD大鼠右膝置入自制人工关节假体,建立人工关节松动的动物模型,分成3组:阴性对照组,阳性对照组和实验组。阴性对照组关节腔内注射磷酸缓冲液与鼠血清混合液,阳性对照组关节腔内注射1010/ml关节磨屑(超高分子聚乙烯颗粒),实验组关节腔内注射1010/ml关节磨屑同时用阿伦膦酸钠灌胃(每日1mg/kg)。术后12周,处死各组动物行组织切片对比观察假体周围骨溶解情况。体外分离培养人外周血单个核细胞并分成5组,A组为单核细胞组,B组为单核细胞和关节磨屑混合培养组,C组为单核细胞和关节磨屑混合培养加入10-4mol/L阿伦膦酸钠,D组单核细胞和关节磨屑混合培养加入10-5mol/L阿伦膦酸钠,E组为单核细胞和关节磨屑混合培养加入10-6mol/L阿伦膦酸钠,检测各组单个核细胞分泌溶骨因子的情况。结果:关节磨屑可引起假体周围骨溶解,刺激单个核细胞分泌溶骨因子,阿伦膦酸钠可阻止这种作用。结论:阿伦膦酸钠可有效防止关节磨屑诱导的人工关节松动,有望用于临床。

Objective ：To investigate the effect of alendronate on the prevention and treatment ofaseptic loosening of prosthesis. Methods：A rat model of particle-induced osteolysis was used. Thirty-xis SD rats were divided into three groups：negative control group, positive control group and experiment group. Alendronate was administered by ig in experiment group. Positive control group and experiment group received intro-articular injections of ultrahigh molecular weight polyethylene （UHMW- PE） particles at 4,6,8,10 weeks postoperatively. Negative control group was received injection with mixture solution of mouse serum and PBS only. All animals were sacrificed at 12 weeks after operation for histologic examination. In vitro human peripheral blood mononuclear （PBMC）were separated and cultured and divided into five groups as group A ：PBMC group,group B. PBMC and particles, group C：PBMC and particles with 10^-4 mol/L alendronate, group D：PBMC and particles with 10^-5 mol/L alendronate, group E：PBMC and particles with 10^-6 mol/L alendronate. The production of IL-1 β ,IL-6,TNF-α in each group were tested. Results： Alendronate could prevent particle-induced osteolysis. The production of IL-1β, IL-6,TNF-α was inhibited when alendronate was used. Condusion.Alendronate can inhibit bone absorptive factors expression induced by wear particles and may be used in the prevention and treatment of aseptic loosening of prosthesis.