不同剂量糖皮质激素对大鼠骨密度和生物力学性能的影响

Effects of glucocorticoid with different dosage on bone mineral density and biomechanical properties in rats

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 exposure to glucocorticoids with different dosage on skeleton of normal 3-month-old rats by dual energy X-ray absorptiometry（ DXA）,biomechanical testing and bone histopathology. Methods Thirty-one 3-month-old female clean level SD rats were randomly divided into 3 GC-treated groups,with tail intravenous injections of dexamethasone（ Dex） at the dosage of 1,2. 5,5 mg / kg twice per week for 8 weeks,respectively,and 1 normal control group treated with saline. At the end of experiment,bone mineral content（ BMC） and bone mineral density（ BMD） of the femur and the 3rd lumbar vertebrae in rats were measured by DXA. The 3-point bending test of the total femur and compression test of the 5th lumbar vertebrae were also conducted,respectively. Microstructure of the trabecula in proximal metaphysis of the tibia was observed by bone pathological section for quantitative analysis. Results Compared with control group,the body weight was significantly decreased in all Dex-treated groups,while no obvious decrease in vertebral BMC,BMD and maximum compressive loads was found. The total femoral BMC was also reduced significantly in all Dextreated groups,while the total femoral BMD,proximal and distal femoral BMD were reduced only in Dex 1mg group. The fracture load,maximum load and elastic load for 3-point bending test were all evidently decreased in Dex 1mg group,while the Dex 2. 5mg group and Dex 5mg group only showed a decline in elastic load. All Dextreated groups showed an unevenly spatial distribution of the trabecula,which indicated a low bone metabolic state. Conclusions The exposure to GC for 8 weeks brings negative effects on skeleton of the 3-month old rats,which will cause more bone loss and worse mechanical properties in femur than in lumbar vertebrae. Higher dosage of Dex does not increase bone mass loss or change the mechanical properties. Both the decline in bone mechanics,especially elastic load,and unevenly density distribution of trabecula indicate that Dex will affect more bone quality other than bone mass. The side effects of GCs on skeleton in clinical application should be evaluated with various methods.