【摘要】 背景:氨基葡萄糖是骨关节炎特异性的治疗药物,有研究表明骨吸收抑制剂阿伦膦酸钠对骨性关节炎具有潜在的治疗作用。目的:探讨阿仑膦酸钠联合盐酸氨基葡萄糖对前交叉韧带切断诱导的兔膝骨性关节炎模型关节软骨和软骨下骨的保护作用及其作用机制。方法:将3月龄新西兰大白兔随机分为假手术组,模型组,盐酸氨基葡萄糖组,联合治疗组。除假手术组外,其余3组动物均右侧膝关节行前交叉韧带切断建立兔膝骨性关节炎模型。建模成功后,模型组用生理盐水治疗;盐酸氨基葡萄糖组给予盐酸氨基葡萄糖灌胃;联合治疗组给予盐酸氨基葡萄糖组灌胃同时,皮下注射阿仑膦酸钠。8周后观察膝关节外观,取所有组兔胫骨去除软骨后行软骨下骨生物力学检测,测定最大载荷和弹性模量,取股骨测量远端1/4骨密度后,用苏木精-伊红染色及"Mankin评分"观察关节软骨退变情况。结果与结论:建模后盐酸氨基葡萄糖组和联合治疗组膝关节出现了轻度骨性关节炎的表现。盐酸氨基葡萄糖组和联合治疗组Mankin评分显著低(P<0.05)。联合治疗组股骨远端骨矿物质密度最高(P<0.05)。盐酸氨基葡萄糖组的最大载荷和弹性模量均显著低于联合治疗组(P<0.05)。实验结果提示,阿仑膦酸钠与盐酸氨基葡萄糖组联合应用可通过保护关节软骨及改善软骨下骨代谢的双重作用,抑制前交叉韧带切断术后兔膝骨性关节炎的发展,且效果优于单纯用盐酸氨基葡萄糖治疗。更多还原

【Abstract】 BACKGROUND: Glucosamine hydrochloride is considered available agent for osteoarthritis, while alendronate, an inhibitor of bone resorption, is reported to be potential for the treatment of osteoarthritis. OBJECTIVE: To study the curative effects and related mechanisms of alendronate combined with glucosamine hydrochloride on the osteoarthritic rabbit knee induced by anterior cruciate ligament transaction. METHODS: New Zealand rabbits, aged 3 months, were divided randomly into sham surgery, model, glucosamine hydrochloride, and glucosamine hydrochloride + alendronate groups. All rabbits were prepared for right knee osteoarthritis model induced by anterior cruciate ligament transaction except that in the sham surgery group. Group glucosamine hydrochloride received a daily administration of glucosamine hydrochloride (150 mg/kg), group glucosamine hydrochloride + alendronate received glucosamine hydrochloride plus a subcutaneous injection of alendronate (10 μg/kg per day); in contrast, animal in the model group received normal saline with the same dose. All rabbits were sacrificed 8 weeks later. Samples of cartilage harvested from right knees were observed for the macro-pathologic changes after the first and the right tibias were removed and biomechanical test was performed to measure the maximal loading and compression modulus. Femurs were prepared for the paraffin section, with the subsequent staining of hematoxylin-eosin staining and graded by Mankin scale. RESULTS AND CONCLUSION: Compared to the model group, rabbits in the glucosamine hydrochloride group and glucosamine hydrochloride + alendronate group showed milder osteoarthritic changes, with significantly lower Mankin scores (P < 0.05). Bone mineral density of distal femur in the glucosamine hydrochloride + alendronate group was significantly higher than those of other groups (P < 0.05). Both the maximal loading and compression modulus in the glucosamine hydrochloride group was significantly lower than those of glucosamine hydrochloride + alendronate group. Alendronate combined with glucosamine hydrochloride had a better effect on anterior cruciate ligament transaction-induced rabbit osteoarthritis by inhibiting the development of osteoarthritis from directly protecting cartilage and modulating subchondral bone metabolism.更多还原