泼尼松灌胃与肌内注射对大鼠骨密度、骨生物力学性能及骨代谢的影响

Comparison of the effects of gastric gavage and intramuscular injection of prednisone on bone mineral density,skeletal biomechanical properties and bone metabolism in rats

目的观察泼尼松灌胃与肌内注射两种不同给药方法对大鼠骨密度、骨生物力学及骨代谢的影响。方法将45只SPF级雄性SD大鼠随机分为3组(正常组15只、灌胃组15只、肌内注射组15只),其中正常组大鼠作为阴性对照,予0.9%生理盐水灌胃2 m L/d;灌胃组大鼠给予泼尼松0.5 mg/(kg·d)灌胃;肌内注射组大鼠给予泼尼松0.5 mg/(kg·d);12周后测定离体的大鼠椎体骨密度及血清β-CTX、PINP水平变化,采用三点弯曲试验测量股骨皮质骨最大载荷、弹性载荷、断裂载荷等生物力学指标。结果与正常组相比,灌胃组及肌内注射组大鼠椎骨骨密度值均显著性降低(P<0.05);与灌胃组相比,肌内注射组大鼠椎骨骨密度显著下降(P<0.05);与正常组相比,灌胃组及肌内注射组大鼠股骨的弹性载荷、最大载荷、断裂载荷均显著降低(P<0.05),肌内注射组与灌胃组大鼠的弹性载荷、最大载荷、断裂载荷相比差异无显著性(P>0.05)。与正常组相比,灌胃组及肌内注射组大鼠中血清β-CTX水平均显著升高(P<0.05)而PINP水平均显著降低(P<0.05),与灌胃组相比,肌内注射组大鼠血清β-CTX水平显著升高(P<0.05)而PINP水平显著降低(P<0.05)。骨组织切片HE染色显示:肌内注射组大鼠的骨小梁明显纤细疏松,造血组织明显减少,脂肪组织明显增多。结论泼尼松对大鼠的骨密度、骨生物力学及骨代谢指标都有影响,而肌内注射泼尼松比口服对骨密度、骨强度、骨代谢的影响更大,更易造成骨质疏松症。因此,建议临床使用泼尼松时选择口服作为给药方式更安全。

Objective To compare the effects of gastric gavage and intramuscular injection of prednisone on the bone mineral density, skeletal biomechanical properties and bone metabolism in rats.Methods A total of 45 SPF rats were randomly divided into three groups：normal group, intragastric administration group, and intramuscular injection group.The normal group, as a control group, was administrated with normal saline 2 mL per day, both the intragastric administration group and i.m.injection group received prednisone 0.5 mg/（kg.d） for 12 weeks.All rats were examined for bone mineral density （BMD） and the level of serum β-CTX and PINP.The femoral cortical biomechanical properties （ elastic load, maximal load, rupturing load） were measured by three point bending test.Results After 12 weeks, compared with the normal group, BMD and elastic load, maximal load, and rupturing load of the femur were significantly decreased.Compared with the intragastric gavage group, BMD was significantly decreased, while the elastic load, maximal load, and rupturing load of the femur were not significantly changed in the i.m.injection group （P〈0.05 for all）.Compared with the normal group, the level of serum β-CTX was significantly raised （P〈0.05） and the level of serum PINP was significantly decreased （P〈0.05）.Compared with the intragastric gavage group, the level of serumβ-CTX was also significantly raised （P〈0.05）, the level of serum PINP was significantly decreased （P〈0.05）, the bone trabecula and hemopoietic tissue were obviously decreased, while the adipose tissue increased obviously. Conclusions Both intragastric gavage and intramuscular injection of prednisone affect the level of BMD, skeletal biomechanical properties and bone metabolism.However, i.m.injection of prednisone decreases the BMD and bone strength more significantly, leading to a higher bone turnover with increased bone resorption, and leads to osteoporosis earlier.Our results may suggest that oral administration of prednisone is more safe in clinical treatment.