摘要目的 利用低氧模拟化合物去铁胺(Deferoxamine)干预1型糖尿病小鼠,观察小鼠骨骼骨密度、骨体积、骨结构、骨强度、骨代谢变化情况.方法 通过腹腔注射链脲佐菌素建立1型糖尿病小鼠模型.实验分为对照组(正常小鼠)、糖尿病组、去铁胺干预组,利用Micro-CT检测小鼠股骨远端松质骨骨密度、骨量、骨结构,利用三点弯曲实验检测小鼠股骨骨强度,苏木精-伊红(HE)染色观察小鼠胫骨骨小梁表面成骨细胞数量,实时定量PCR检测小鼠胫骨骨组织runt家族相关基因2(Runx-2)、骨钙素、抗酒石酸酸性磷酸酶(TRAP) mRNA变化水平,Western印迹检测小鼠胫骨骨组织低氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)蛋白表达水平.结果 与对照小鼠相比,糖尿病小鼠的骨体积、骨密度、骨强度下降,骨结构破坏;去铁胺干预后能够在一定程度上提高糖尿病小鼠骨体积、骨密度、骨强度,同时骨结构得到部分恢复.去铁胺干预后糖尿病小鼠松质骨表面成骨细胞数量增多,骨组织内Runx-2、骨钙素、TRAP mRNA表达增高,HIF-1α、VEGF蛋白表达增多(P＜0.05).结论 去铁胺能够通过激活低氧诱导因子信号通路促进骨形成,从而部分阻止1型糖尿病小鼠骨质疏松形成.

abstractsObjective To observe the effect of a hypoxia mimicking agent deferoxamine (DFO) on the mineral density,volume,architecture,strength,and metabolism of the bones in type 1 diabetic mice withosteoporosis.Methods Type 1 diabetic mice model was established by intraperitoneal injections of streptozotocin.The mice were divided into control (normal mice),diabetes mellitus,and DFO groups.Micro-CT was used to analyze the bone mineral density,volume,architecture,and strength of the trabecule in the distal part of femurs.Three point bending test was carried out to evaluate the bone strength.Hematoxylin and eosin (HE) staining was performed to observe the alteration in the number of osteoblasts.Real-time PCR was used to detect the mRNA expressions of Runt-related gene 2 (Runx-2),osteoclacin,and tartrate resistant acid phosphatase (TRAP) in tibias.Western blot was used to detect the protein expressions of Hypoxia-inducible factor-1α(HIF-1α) and vascular endothelial growth factor (VEGF) in tibias.Results There was a decrease in mineral density,volume,strength of bones as well as deteriorated trabecular microarchitecture in diabetic mice as compared to control mice,which were partially improved by DFO treatment.Moreover,DFO treatment increased the number of osteoblasts and mRNA expression levels of Runx-2,osteoclacin,TRAP,as well as protein expression levels of HIF-1 α and VEGF(P＜0.05).Conclusion Bone loss could be partially prevented by DFO treatment in type 1 diabetic osteoporosis mice,which might be ascribed to increased bone formation via stimulating hypoxia inducible factor singnaling pathway.