辛伐他汀对丙戊酸钠干预下骨质疏松伴骨缺损愈合的影响

Effects of simvastatin on osteoporosis with bone defect healing in rats induced by sodium valproate

目的:探讨辛伐他汀(SIM)对丙戊酸钠(SVP)干预下骨质疏松大鼠的股骨骨缺损愈合的影响。方法:SPF级健康雌性SD大鼠40只,行双侧去卵巢手术(OVX)。随后在剩余大鼠双侧股骨干骺端建立直径2.5 mm的圆形骨缺损并将其随机分为3组,OVX组、SVP组、SVP+SIM组。所有大鼠在药物干预8周后行安乐死,收集股骨分别行Micro-CT扫描、骨应力学测试及骨组织切片染色分析。结果:SVP组与OVX组相比,大鼠股骨骨密度以及骨应力强度降低,股骨骨缺损延迟愈合,骨组织OCN、Col I表达下降;SVP+SIM组与SVP组相比骨组织的强度更高,股骨骨缺损恢复效果更佳,且OCN、Col I水平提高。结论:SVP治疗后的大鼠股骨骨密度以及骨应力强度降低,股骨骨缺损延迟愈合;而SIM的治疗可有效逆转SVP对骨质的负面效应,增强各组大鼠的骨密度及骨骼强度,促进大鼠股骨骨缺损愈合。

Objective:To observe the effect of simvastatin(SIM)on osteoporosis with defect healing of bone in rat models treated by sodium valproate(SVP).Methods:Forty healthy female SD rats(SPF grade)were used to develop the animal models by bilateral ovariectomy(OVX).Round bone defects measuring 2.5 mm in diameter were created at the epiphysis of bilateral femora.Then the experimental rats were divided into OVX group,SVP group and SVP plus SIM group.All rats were euthanized at week 8 after treatment.Distal femurs were harvested,and undergone scanning by Micro-CT,biomechanical test and histological analyses.Results:Decreased density of the femurs and bone tissue strength,delayed healing of the bone defects and down-regulated OCN and Col I levels were seen in SVP group compared to OVX group.Rats in SVP+SIM group had higher bone tissue strength,better reversed femoral bone defects and improved OCN and Col I expression than those in SVP group.Conclusion:Treatment with sodium valproate may lead to decreased bone mineral density and bone strength as well as delayed healing of bone defects in rats,whereas simvastatin can effectively counteract the negative effect of bone defect from SVP therapy,and improve the osteogenesis as well as the healing of the bone defects.