【摘要】 目的 :通过兔糖皮质激素性骨质疏松症(glucocorticoid-induced osteoporosis,GIOP)模型,探讨培哚普利对GIOP的干预作用以及其具体机制。方法 :10月龄雄性新西兰大白兔(3.0~3.5 kg)45只,采用随机数字表的方法将其随机分成3组:正常对照组(肌肉注射生理盐水,n=15,NC组)、模型组(肌肉注射地塞米松,n=15,GIOP组)和治疗组(肌肉注射地塞米松+口服培垛普利,n=15,GIOP+ACEI组);所有动物于干预后12周处死取材。通过检测骨组织形态计量学、生物力学以及骨代谢相关的血清学指标和m RNA表达来分析各组骨质和骨量的变化。结果:12周时骨形态计量学及生物力学结果显示GIOP组的骨量以及骨强度明显低于NC组(P<0.05);在给予培哚普利干预后,GIOP+ACEI组的骨量及骨强度较GIOP组明显增高(P<0.05)。与NC组比较,GIOP组矿化表面积、矿化沉积率、血清骨钙素均明显下降而破骨细胞数量、破骨细胞表面积、侵蚀表面积以及尿脱氧吡啶啉均明显增高(P<0.05),而给予培哚普利干预后这些指标的变化明显改善(P<0.05)。实时定量PCR结果显示给予地塞米松干预后SOST的m RNA表达以及RANKL/OPG的m RNA水平的比值均较NC组明显增高(P<0.05),而Runx2的m RNA水平明显下降(P<0.05);当给予培哚普利干预后,这些m RNA表达的变化被明显改善(P<0.05)。结论:培哚普利可以促进骨形成和抑制骨吸收,从而有效的干预糖皮质激素性骨质疏松症的发生,这为糖皮质激素性骨质疏松症的预防和治疗提供了新的思路。更多还原

【Abstract】 Objective: To investigate the role of perindopril for prevention and treatment of glucocorticoid induced osteoporosis(GIOP) in rabbits. Methods:A total of 45 male New Zealand white rabbits(10 months old,weight 3.0 to 3.5 kg) were randomly divided into 3 groups involving normal control group(muscle injection of saline solution,n=15,group NC),model group(muscle injection of dexamethasone,n=15,group GIOP),and treatment group(muscle injection of dexamethasone combined with oral perindopril,n=15,group GIOP+ACEI). All rabbits put to death after 12 weeks’ treatment. The changes of bone mass and strength were observed and analyzed by bone histomorphology,biomechanics,metabolic bone related serological indexes and m RNA expression. Results:At 12 weeks,the analysis of bone histomorphology and biomechanics results showed that the bone mass and bone strength of group GIOP were significantly lower than that of group NC(P<0.05);after perindopril treatment,the bone mass and bone strength of group GIOP+ACEI were higher obviously than that of group GIOP(P<0.05). Mineralizing surface,mineral apposition rate and serum osteocalcin in group GIOP decreased than group NC; however,osteoclast number,osteoclast surface,eroded surface,and urinary deoxypyridinoline in group GIOP increased than group NC(P<0.05);these changes were inhibited after perindopril treatment(P <0.05). Quantitative RT-PCR revealed that after dexamethasone treatment,the ratio of SOST m RNS expression and RANKL / OPG m RNA expression obviously increased than that of group NC(P<0.05);and Runx2 expression decreased significantly(P<0.05);while the changes of m RNA expression were improved by perindopril treatment. Conclusion: Perindopril can promote bone formation and inhibit bone resorption to deduce glucocorticoid induced osteoporosis. This study provides a new method for prevention and treatment of GIOP.更多还原