骨质疏松大鼠股骨内单次注射辛伐他汀强化骨骼的实验研究  

Bone augmentation in an osteoporosis rat model via a single local injection of simvastatin

作　　者：杨宁[1] 崔岳毅[1] 韩晓光[1] 冷慧杰 陈仲强[1] 刘忠军[1] 党耕町[1] 宋纯理[1] 

机构地区：[1]北京大学第三医院骨科,100191 [2]北京脊柱外科研究所北京市重点实验室

出　　处：《中华骨科杂志》2012年第5期500-506,共7页Chinese Journal of Orthopaedics

基　　金：国家自然科学基金（81171693,81100895）;教育部新世纪优秀人才支持计划（NCET-10-0202）

摘　　要：目的研究骨质疏松骨骼局部注射辛伐他汀刺激成骨的效果，探索疏松骨骼局部给药预防脆性骨折的治疗方法。方法36只3月龄雌性SD大鼠双侧卵巢切除后加低钙饮食3个月，制备大鼠骨质疏松模型。实验大鼠随机分为3组，每组12只，分别在实验大鼠的左侧股骨髓腔内单次注射辛伐他汀溶液5mg、10mg，对照组单纯注射空白载体。分别在术后1个月及术后5个月每组随机处死半数大鼠（n-6）并取材。双能X线骨密度仪测定骨密度、Micro—CT扫描并定量分析骨组织形态改变、骨生物力学测试研究骨骼力学性能的变化。结果辛伐他汀局部注射后1个月和5个月，辛伐他汀注射组的骨密度、骨微结构参数如骨皮质厚度、骨小梁密度及连接率明显优于对照组，股骨髁及股骨颈的力学性能明显高于对照组。单次注射辛伐他汀的局部骨强化效果至少持续5个月，对照组骨量则持续丢失，力学性能持续降低。结论疏松骨骼单次注射小剂量辛伐他汀可强效而持久地促进皮质骨形成及骨小梁改建，改善骨骼微结构，增加骨密度及骨强度，可作为强化局部、防治骨质疏松骨折的新选择。Objective To explore the bone anabolic effects after a single local injection of simvastatin into femoral cavities of osteoporotic rats. Methods Thirty-six female SD rats （3 months old, body weight 250-300 g） were ovariectomized （OVX） and low-calcium-diet fed for 3 months, OVX rats were randomized into 3 groups （n-12）. Left femurs of group A, B and C were injected with 0, 5 and 10 mg simvas tatin, respectively. Half of the rats in each group were randomly euthanized separately 1 and 5 months after simvastatin injection. Left femurs were taken out for bone mineral density （BMD） assessment with dual ener- gy X-ray absorptiometry, bone histomorphometic changes were analysized by Micro-CT, and two kinds of biomechanical tests were used to evaluate the osteogenic effects. Results One and five months after injection, BMD in mid-diaphysis significantly increased in simvastatin-injected groups compared to the control group. For Micro-CT analysis, significant increase in total bone volume/total tissue volume, cortical wall thickness, trabcular thickness, trabecular number, and a significant decrease in trabecular spacing were observed in simvastatin-injected groups compared to the control group. For both biomechanics （the three-point- breaking test of condyles and axial compressive testing of proximal femur）, the values were significantly high- er in simvastatin-injected groups than the control group. Conclusion Local simvastatin treatment showed a positive effect on improving mechanical strength, structure of osteopenic femurs and BMD. Our findings may provide a new strategy for the prevention and treatment of osteoporosis, especially for osteoperotic fractures.

关 键 词：骨质疏松 投药 局部 骨生成 

分 类 号：R580[医药卫生—内分泌]