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目的通过双能X射线骨密度仪(dual energy X-ray absorptiometry,DXA)、骨生物力学测试及骨组织计量学等方法研究不同剂量糖皮质激素摄入对正常3月龄大鼠骨骼的影响。方法 31只SPF级3月龄SD雌性大鼠,随机分为正常对照组、地塞米松(Dex)1、2.5、5 mg/kg组,每周尾静脉注射给药2次,共8周,对照组给予生理盐水对照。给药结束后,离体股骨和第3腰椎通过DXA进行骨矿含量(bone mineral content,BMC)、骨矿密度(bone mineral density,BMD)测定,全股骨和第5腰椎分别进行三点弯曲和压缩力学实验,并通过骨组织病理切片观察胫骨近端骨小梁的显微结构并定量分析。结果与正常组相比,所有激素组大鼠体重均明显降低,腰椎BMC、BMD及最大压缩载荷均未明显下降,全股骨BMC均有所降低,但只有Dex 1 mg组全股骨和股骨远端、近端BMD降低;Dex 1 mg组三点弯曲实验断裂载荷、最大载荷和弹性载荷都明显降低,而Dex 2.5 mg、Dex 5 mg组只有弹性载荷仍低于正常对照组。激素组骨小梁有空间密度分布不均现象,骨代谢处于低转换。结论应用糖皮质激素8周对3月龄大鼠骨骼的不利影响股骨较腰椎明显,股骨骨量丢失,力学性能下降,两者均无剂量依赖性。更高剂量Dex并没有增加骨量丢失和力学性能改变。力学性能特别是弹性载荷下降以及骨小梁密度分布不均,提示糖皮质激素更多的是引起骨质量下降。临床上应用糖皮质激素时,应使用多种方法评价其对骨骼的副作用。
Objective To investigate the effects of different doses of glucocorticoid on bones in normal 3-month-old rats by dual energy X-ray absorptiometry (DXA), bone biomechanical test and bone histomorphometry. Methods Thirty-one female Sprague-Dawley (SD) rats of 3-month-old SD were randomly divided into normal control group, Dex 1,2,5,5 mg / kg group and twice weekly injection of tail vein for 8 weeks. The control group was given saline control. After the administration, the bone mineral content (BMC) and bone mineral density (BMD) of the femur and the third lumbar vertebra were measured by DXA. The total femur and the fifth lumbar vertebrae were subjected to three-point bending and Compressive mechanics experiments were performed. The microstructure of trabecular bone in the proximal tibia was observed and quantified by histopathological examination. Results Compared with the normal control group, the body weight of all the rats in the hormone group decreased significantly. The BMC, BMD and maximum compressive load of the lumbar vertebrae were not significantly decreased. The total femoral BMC was decreased. However, only the total femur and femur distal to the Dex 1 mg group , And the proximal BMD decreased. The ultimate load and the ultimate load of Dex 1 mg group at 3-point bending test decreased significantly. However, the elastic load of Dex 2.5 mg and Dex 5 mg group was still lower than that of the normal control group. Hormone trabecular bone density distribution of spatial heterogeneity, bone metabolism in the low conversion. Conclusion The detrimental effects of glucocorticoids on skeletal bone of 3-month-old rats after 8 weeks of glucocorticoid treatment were obvious compared with those of lumbar spine. The femoral bone loss and mechanical properties decreased, both of which were dose-dependent. Higher doses of Dex did not increase bone loss and altered mechanical properties. Mechanical properties, especially the decline in elastic load and the uneven distribution of trabecular bone density, suggesting that glucocorticoid more is caused by decreased bone quality. Clinical application of glucocorticoids, there should be a variety of ways to evaluate its side effects on the skeleton.