培哚普利对兔糖皮质激素性骨质疏松症干预作用的实验研究  

Investigation on the role on perindopril for prevention and treatment of glucocorticoid induced osteoporosis in rabbits

作　　者：周峰[1] 荣春[2] 王恺 王春生[4] 张永涛[1] 

机构地区：[1]青岛大学附属医院骨科,山东青岛266061 [2]青岛大学附属医院手术室,山东青岛266061 [3]青岛市海慈医疗集团,山东青岛266033 [4]西安交通大学第二附属医院骨科,陕西西安710004

出　　处：《中国骨伤》2016年第1期52-57,共6页China Journal of Orthopaedics and Traumatology

基　　金：国家自然科学基金资助项目(编号:81472067)~~

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。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.

关 键 词：糖皮质激素性骨质疏松症 骨代谢 培哚普利 兔 

分 类 号：R681[医药卫生—骨科学]