辛伐他汀联合利塞膦酸钠对尾悬吊诱导小鼠骨丢失的作用  

Effects of risedronate sodium combined with simvastatin on tail suspension-induced bone loss in mice

作　　者：范新昊 田发明 王婧瑶 张楠[1] 迟博婧 张国彬 郭志斌 FAN Xinhao;TIAN Faming;WANG Jingyao;ZHANG Nan;CHI bojing;ZHANG Guobin;GUO Zhibin(KaiLuan General Hospital,Tangshan 063000,China;North China University of Science and Technology,Tangshan 063000;KaiLuan Linxi Hospital,Tangshan 063000)

机构地区：[1]开滦总医院,河北唐山063000 [2]华北理工大学,河北唐山063000 [3]开滦总医院林西矿医院,河北唐山063000

出　　处：《中国比较医学杂志》2019年第11期58-64,115,共7页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(81773327);河北省自然科学基金(H2013209255);河北省医学科学研究重点课题(20160722)

摘　　要：目的 探讨和比较单独或联合应用辛伐他汀和利塞膦酸钠对地塞米松诱导的小鼠骨质疏松的作用。方法 12周龄雌性C57BL6小鼠30只,随机分成5组(每组6只):对照组(A组)、模型组(B组)、辛伐他汀组(C组)、利塞膦酸钠组(D组)和联合干预组(E组)。除A组外,通过尾悬吊制备小鼠骨质疏松模型,C、D、E组分别给予辛伐他汀(5 mg/(kg·d))、利塞膦酸钠(1 mg/(kg·d))和两者联合干预,3周后处死取材。微计算机断层扫描技术(micro-CT)检测左侧胫骨近端松质骨和皮质骨骨量及微结构参数,三点弯曲实验分析左侧股骨生物力学性能。提取右侧胫骨RNA,实时荧光光定量聚合酶链反应(PCR)检测OPG和RNAKL的表达,提取右侧股骨蛋白,Western blot法检测OPG和RNAKL蛋白的表达。结果 Micro-CT:B组骨小梁体积比(BV/TV)、骨小梁数量(Tb.N)显著低于其余各组,骨小梁分离度(Tb.Sp)显著高于其余各组(P<0. 05),C、D组BV/TV显著低于A、E组,Tb. Sp显著高于A组(P<0. 05);(2)生物力学:最大载荷、弹性模量B组显著低于A、E组(P<0. 05)、其余各组间比较无统计学差异(P>0. 05);(3)PCR检测结果:OPG的mRNA表达在C、E组显著高于B组(P<0. 05);RNAKL在B组表达显著高于A组(P<0. 05);(4)Western blot:OPG在A组的表达显著高于其余各组(P<0. 05),E组显著高于B组(P<0. 05);RANKL在A组的表达显著低于其余各组(P<0. 05)。结论 尾悬吊可以造成小鼠骨丢失和骨质量下降,辛伐他汀和利塞膦酸钠联合应用能阻止该模型骨丢失和骨质量下降,效果优于单独用药。Objective To compare the efficiency of single or combined application of simvastatin and risedronate sodium on a disused osteopenia rat model with tail suspension.Methods Thirty 12-week-old C57BL6 mice were assigned to five groups of six mice each:control(A),tail suspension(B),simvastatin treatment(C),risedronate sodium treatment(D),and combined treatment(E).All but group A received tail suspension,and the groups were treated with the vehicle,simvastatin(5 mg/(kg·d)),risedronate sodium(1 mg/(kg·d))or a combination of both,respectively.All mice were sacrificed after 3 weeks.Micro-CT was performed on the left tibia to determine the bone mass and microstructure of both the trabecular and cortical bones.Three-point bending test was used for biomechanical analysis of the left femur.The right tibias were subjected to RNA extraction and PCR analysis of OPG and RANKL expression,and the right femurs were used for protein level detection by western blot.Results Micro-CT:BV/TV and Tb.N in group B were significantly lower than those of the other groups(P<0.05),the Tb.Sp in group B was significantly higher than that of the other groups.BV/TV in groups C and D were significantly lower than those in groups A and E,while Tb.Sp in groups C and D was significantly higher than that in group A(P<0.05).②Biomechanical test:maximal loading and the elastic modulus in group B were significantly lower than those of groups A and E(P<0.05).③PCR:the mRNA level of OPG in groups C and E was significantly higher than that in group B(P<0.05),and RANKL was expressed significantly higher in group B than that in group A(P<0.05).④Western blot:the protein level of OPG in group A was markedly higher than that in the other groups(P<0.05),OPG in group E was significantly higher than that in group B(P<0.05),and the protein level of RANKL in group A was significantly lower than that in the other groups(P<0.05).Conclusions Tail suspension caused bone loss and deterioration of bone quality in mice,and simvastatin combined with risedronate sodium tre

关 键 词：利塞磷酸钠 辛伐他汀 骨丢失 生物力学 微结构 小鼠 

分 类 号：R-33[医药卫生]