骨质疏松大鼠尾椎局部单次注射辛伐他汀强化骨骼的实验研究

摘要

Objective To investigate the effect of local injection of simvastatin in the caudal vertebra on stimulating bone augmentation in osteoporotic rats, and to explore the treatment of local medication in osteoporotic vertebrae, strengthening of key point, and the prevention of fragility fractures. Methods Thirty-six 3 - month-old female SD rats were ovariectomized ( OVX ) and fed with low-calcium-diet for 3 months, in order to acquire the model of osteoporotic rats. All the rats were randomly divided into 3 groups, with 12 rats in each group. Blank vector, 1 mg, and 2 mg simvastatin was once injected into the caudal vertebrae 5-7 (C5 -C7) of experimental rats. Half of the rats ( n = 6 ) in each group were randomly sacrificed on the 12 or 24 days after injection. The samples were collected for histomorphormetry and bone mechanical analysis using micro-CT and biomechanical method. Results On the 12 days after the injection of simvastatin, bone microstructural parameters including cortical wall thickness ( CWT ), bone trabecular density, and the connection rate in simvastatin group were superior to those in control group, and the mechanical property of vertebrae was better than that in control group. The effect on the 24 days after injection still remained obvious. Conclusion Single injection of small dose of simvastatin ( 1 mg or 2 mg ) in the caudal vertebrae in osteoporotic rats can rapidly and effectively promote the formation of bone cortex and the reconstruction of bone trabecula. It also can ameliorate the bone microstructure and improve bone strength. It may be a new choice for the treatment of local strengthening and the prevention of vertebral osteoporotic fractures.%目的 研究骨质疏松大鼠尾椎局部注射辛伐他汀刺激成骨的效果,探索疏松椎体局部给药,重点强化,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,分别在实验大鼠的第5、6、7尾椎内(C5-C7)单次注射空白载体、辛伐他汀溶液1mg、2 mg.分别在术后12天及24天每组随机处死半数大鼠(n=6)并取材.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仅12天辛伐他汀注射组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,椎体力学性能明显高于对照组,术后24天效果依然明显.结论 骨质疏松大鼠尾椎单次注射小剂量辛伐他汀(1mg与2 mg)可快速、强效地促进皮质骨形成及骨小梁改建,改善骨骼微结构,提高骨强度,可作为强化局部、防治椎体骨质疏松骨折的新选择.