Micro-CT和力学测试观察环磷酰胺诱导大鼠骨质疏松模型的时效特点

The observation of time-effect relationship in cyclophosphamide-induced rat osteoporosis model using micro CT and biomechanical test

目的应用骨生物力学测试和micro-CT技术,观察环磷酰胺诱导大鼠骨质疏松的时效关系。方法 3月龄SPF级雄性SD大鼠用环磷酰胺4.5 mg·kg-1·d-1连续灌胃15 d,停药后的0、15和30 d,取右侧股骨进行生物力学检测,然后进行MicroCT扫描及三维重建。结果大鼠环磷酰胺诱导15 d后,股骨松质骨的三维结构和评价参数均呈现明显的微观结构退化,小梁骨结构由板状向杆状变化,而生物力学性能降低,骨脆性增加,骨折风险增加。停药后15d和30d,股骨松质骨的三维结构和评价参数仍然呈现明显的骨质疏松变化,除韧性系数和刚性系数外,其他生物力学参数仍然低下。停药后,环磷酰胺组大鼠以上各骨评价参数虽呈现了稳定的增长趋势,但较正常大鼠明显减弱。结论环磷酰胺诱导的大鼠骨质疏松模型近期效果好,停药后1个月内,骨增长的抑制效果虽有所减弱,但骨丢失仍然明显。

Objective To investigate the time-effect relationship in cyclophosphamide-induced osteoporosis in rats using micro-CT and biomechanical test. Methods Three-month-old male Sprague-Dawley rats were treated with cyclophosphamide （4. 5 mg.kg -1· d-1 ） orally once a day for successive 15 days. After drug withdrawal for 0, 15, and 30d, micro-CT and biomechanical test were performed and the 3D reconstruction was analyzed in the right femur. Results After 15d cyclophosphamide induction, the threedimensional structure and the evaluation parameters of the cancellous bone in the femur presented obvious microstructure degradation in rats. The biomechanical performance of the femur reduced, while the bone fragility and fracture risks increased. After drug withdrawal for 15d or 30d, the three-dimensional structure and the evaluation parameters of cancellous bone in the femur still displayed apparent osteoporotic feature. Except for the rigidity modulus and toughness index, other biomechanical parameters were similar to those in the cyclophosphamide-induced rats. After drug withdrawal, assessment parameters of the cancellous bone and mechanical property of the rat femur showed a stable increase in the cyclophosphamide-induced rats. However, the increase trend was obviously weaker than that in normal rats. Conclusion The cyclophosphamide-induced osteoporosis rat model shows good performance in short-term investigation. Inhibition of bone growth weakens after 1 - month drug withdrawal but bone loss is still obvious.