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[目的]观察唑来膦酸(zoledronic acid,ZOL)干预骨关节炎(osteoarthritis,OA)软骨下骨改变及关节软骨退变的效果,探讨ZOL抑制早期OA病情进展的可能机制,为ZOL干预早期OA的疗效评价提供动物实验依据。[方法]32只新西兰兔随机分为四组:唑来膦酸高剂量组(A组)、唑来膦酸中剂量组(B组)、唑来膦酸低剂量组(C组)、安慰剂组(D组),每组8只。A、B、C组造模术后分别于耳缘静脉推注ZOL 250 ug/kg、50 ug/kg、10 ug/kg,D组推注生理盐水2 ml。造模后0、4、8周行DXA扫描,8周行MRI扫描后处死实验动物,取双侧膝关节制作病理组织学切片,比较各组膝关节影像学表现、大体形态及病理变化,并采用Mankin评分进行定量分析。[结果]造模后0、4、8周实验侧膝关节骨密度降低程度A组B组>C组>D组。大体标本及组织切片观察A组OA程度最轻,B、C组较重,D组最重。右膝关节Mankin评分A、B、C、D组分别为(3.67±0.82)、(4.83±1.17)、(6.33±1.21)及(7.50±1.52)。[结论]ZOL静脉注射能够增加软骨下骨骨量,改善微观结构,减轻兔膝关节不稳定诱发的OA关节软骨退变。干预效果与剂量相关,250 ug/kg、50 ug/kg组手术侧骨关节炎病变程度均较轻。
[Objective] To observe the effect of zoledronic acid (ZOL) on the subchondral bone changes and the degeneration of articular cartilage in osteoarthritis (OA) and to explore the possible mechanism of ZOL inhibiting the progression of early OA. Evaluation of the efficacy of OA to provide animal experimental basis. [Methods] Thirty-two New Zealand white rabbits were randomly divided into four groups: high dose ZOL group (group A), ZOL group (group B), low dose ZOL group (group C) Group D (group D), 8 rats in each group. Groups A, B and C were injected ZOL 250 ug / kg, 50 ug / kg and 10 ug / kg respectively in the marginal ear veins after modeling. Group D was given 2 ml normal saline. DXA scans were performed at 0, 4, and 8 weeks after modeling. The rats were sacrificed 8 weeks after MRI scans, histopathological sections of bilateral knees were made and the knee joint imaging findings, gross morphology and pathological changes were compared Mankin score was used for quantitative analysis. [Result] The bone densities of experimental knee reduced at 0, 4, and 8 weeks after model establishment in group A B group> C group> D group. Gross specimens and histological sections were observed in group A with the lightest degree of OA, group B and C heavier and group D heaviest. The Mankin scores of the right knee joint were (3.67 ± 0.82), (4.83 ± 1.17), (6.33 ± 1.21) and (7.50 ± 1.52) in group A, B, C and D, respectively. [Conclusion] Intravenous injection of ZOL can increase the subchondral bone mass, improve the microstructure and reduce the degeneration of OA articular cartilage induced by the instability of rabbit knee joint. The effect of intervention was dose-dependent. The lesion degree of surgical side osteoarthritis in 250 ug / kg and 50 ug / kg groups was lighter.