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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 observe the effects of two different administrations of prednisone and intramuscular injection on bone mineral density, bone biomechanics and bone metabolism in rats. Methods Forty-five SPF male Sprague-Dawley rats were randomly divided into 3 groups (15 in normal group, 15 in gavage group and 15 in intramuscular group). Normal rats were used as negative control and 0.9% saline irrigation Stomach 2 m L / d; gavage group rats given prednisone 0.5 mg / (kg · d) intragastric administration; intramuscular injection of prednisone given 0.5 mg / (kg · d); 12 weeks after the test Vertebral bone density and serumβ-CTX, PINP levels were measured in vitro. The three-point bending test was used to measure the biomechanical parameters such as maximum load, elastic load and fracture load of femur cortical bone. Results Compared with the normal group, the vertebral bone mineral density of the rats in the intragastric administration group and the intramuscular injection group decreased significantly (P <0.05). Compared with the intragastric administration group, the BMD of the vertebral bone in the intramuscular injection group decreased significantly (P <0.05). Compared with the normal group, the elastic load, the maximum load and the fracture load of the femur in the intragastric and intramuscular injection groups were significantly decreased (P <0.05) The elastic load, the maximum load, the fracture load was no significant difference (P> 0.05). Compared with the normal group, the levels of β-CTX in the gavage group and the intramuscular group were significantly increased (P <0.05) and the PINP levels were significantly decreased (P <0.05) The level of β-CTX in the intramuscular injection group was significantly increased (P <0.05) and the level of PINP was significantly decreased (P <0.05). HE staining showed that the trabecular bone of the intramuscular injection group was obviously slender and loose, the hematopoietic tissue was significantly reduced and the adipose tissue was obviously increased. Conclusion Prednisone had an effect on the bone mineral density, bone biomechanics and bone metabolism in rats, and the effect of prednisone intramuscular injection was greater than that of oral administration on bone mineral density, bone strength and bone metabolism, and more likely to cause osteoporosis disease. Therefore, it is safer to choose orally as a mode of administration when using prednisone clinically.