阿仑膦酸钠对大鼠骨关节炎影响的实验研究

Effects of Alendronate on Osteoarthritis in Rats

目的:探讨阿仑膦酸钠(ALN)灌胃对实验性大鼠骨关节炎(OA)的影响。方法:40只大鼠分为5组:正常对照组;模型对照组;ALN小、中、大剂量组(每周0.12,0.6,3.0 mg/kg)。4%木瓜蛋白酶关节腔注射建立大鼠OA模型,造模4周后,ALN组行灌胃治疗,每3 d一次,每次灌胃2 ml,对照组和模型组灌胃等量生理盐水。给药7周后处死,大体形态学、组织学、生化及免疫组化的方法评价关节软骨的情况。结果:组织形态学观察,见ALN中、大剂量组均较模型对照组关节软骨损害减轻,Mankin’s评分及关节软骨基质金属蛋白酶3、9和基质金属蛋白酶抑制剂1的表达均较模型对照组显著降低(P<0.01);与模型组比较,ALN中、大剂量组还显著防止了蛋白多糖的减少(P<0.01),且上述指标ALN大剂量组均较中剂量组更显著。结论:阿仑膦酸钠能有效防治大鼠实验性OA,其效应在一定范围内呈剂量依赖性;其机制可能与抑制关节软骨基质金属蛋白酶表达,防止蛋白多糖的减少有关。

Objective： To explore the effects of Alendronate （ALN） on experimental osteoarthritis in rats. Methods： Animal models of osteoarthritis were obtained in rats by intra-articular injection of 4% chymopapain for three times. Forty rats were divided into five groups （eight in each group） as normal group,model group and three ALN treatment groups （0. 12, 0.6 and 3.0 mg/kg per week orally）. Both normal group and model group were fed with normal saline. All animals were killed after being treated for seven weeks. Cartilage changes were evaluated. Macroscopic, histo- logical, chemistry and immuno-histologic analysis were performed on the articular cartilage. Results： ALN was chondro-protective at high concentration in histology. AI.N in a dosage of 0.6 mg/kg or 3.0 mg /kg per week reduced the expression of matrix metalloproteinases 3, -9, and tissue inhibitor of metalloproteinase-1（P〈0.01） in a dose-dependent manner, furthermore, they prevent the reduction of proteoglycan （PG） contents（P〈0. 01） in a dose-dependent manner. Conclusion： ALN appears to provide some chondro-protection in a dose-dependent manner in this model. The mechanisms are related to the reduction of expression of matrix metalloproteinases-3, -9, and tissue inhibitor of metaltoproteinase-1, and preventing the reduction of proteoglycan con tents.