唑来膦酸联合胰岛素促进2型糖尿病并发雌激素缺乏大鼠骨折早期愈合

目的探讨唑来膦酸联合胰岛素对于2型糖尿病并发雌激素缺乏大鼠早期骨折愈合的影响。方法 32只雌性SD大鼠随机分为CF、DOF、DOFI和DOFIZ 4组。除CF组外,其余3组建立2型糖尿病并发雌激素缺乏动物模型,其中DOFI组和DOFIZ组分别给予单独胰岛素或联合唑来膦酸治疗,骨折后3周取材。通过对骨痂X线片、Micro-CT、番红O-固绿染色、TRAP阳性破骨细胞密度、OCN和Caspase-3的表达进行分析,评价单独应用胰岛素或联合唑来膦酸对其早期骨折愈合的影响。结果DOF组骨痂的骨折愈合X线评分、Tb.N、BV/TV、骨性骨痂面积比和OCN表达均显著低于CF组(P0.05),Th.Sp、TRAP阳性破骨细胞密度和Caspase-3表达均显著高于CF组(P0.05)。胰岛素干预后,DOFI组以上各受损指标中除了Th.Sp外均得到显著改善(P0.05)。联合唑来膦酸干预后,DOFIZ组骨痂面积、Tb.N、BV/TV和骨性骨痂面积比显著高于DOFI组(P0.05),Th.Sp和TRAP阳性破骨细胞密度显著低于DOFI组(P0.05)。结论胰岛素联合早期单剂量唑来膦酸干预可促进2型糖尿病并发雌激素缺乏大鼠骨折早期愈合。

Zoledronic acid combined with insulin promotes early fracture healing in type 2 diabetic rats with estrogen deficiency

Objective To investigate the effect of zoledronic acid combined with insulin on the early stage fracture healing in type 2 diabetic rats with estrogen deficiency. Methods Thirty-two female SD rats were randomly divided into the CF, DOF, DOFI, and DOFIZ group. Except for CF group, rats in the other 3 groups were induced to develop type 2 diabetes and estrogen deficiency animal model. The rats in DOFI and DOFIZ groups received insulin alone or combined with zoledronic acid, respectively. All rats were killed at 3 weeks post-fracture. X-ray, micro-CT, safranine O-fast green staining, TRAP-positive cell density, OCN, and Caspase-3 expression in the callus were analyzed to evaluate the effect of insulin alone or combined with zoledronic acid on the early stage of fracture healing in rats. Results The radiographic healing score, Tb.N, BV/TV, mineralized area per periosteal callus area, and OCN expression in the DOF group were significantly lower than those in CF group (P<0.05), and Th.Sp, TRAP-positive cell density, and the expression of Caspase-3 in the callus were significantly higher than those in CF group (P<0.05). After insulin intervention, all the above parameters in DOFI group were significantly improved except Th.Sp (P<0.05). After insulin combined with zoledronic acid intervention, the callus area, Tb.N, BV/TV, and mineralized area per periosteal callus area in DOFIZ group were significantly higher than those in DOFI group (P<0.05), and the Th.Sp and TRAP-positive cell density were significantly lower than those in the DOFI group (P<0.05). Conclusion Insulin combined with early single dose of zoledronic acid promotes early fracture healing in type 2 diabetic rats with estrogen deficiency.