12周是使用卵巢切除法建立雌性 C57/BL6 J成年小鼠绝经后骨质疏松模型的合适时机

摘要

目的 评估成年C57/BL6J雌性小鼠行卵巢切除术后不同时间点骨密度及松质骨的变化,探讨使用卵巢切除法建立雌性C57/BL6J成年小鼠绝经后骨质疏松模型的合适时机.方法 将60只成年C57/BL6J雌性小鼠随机平均分为8周去势组及12周去势组;前者于8周,后者于12周行双侧卵巢切除术.两组均于手术当天,术后6周、8周、10周及12周各随机抽取6只小鼠进行检测.使用DEXA测量小鼠全身、脊柱及下肢骨密度,并使用micro-CT重建胫骨近端的三维图像及计算松质骨微结构参数.结果 两组小鼠使用DEXA测量的组内各时间点的全身、脊柱及下肢骨密度相比均无统计学差异. micro-CT的结果显示:与8周相比,12周小鼠的胫骨近端松质骨骨量有显著的上升(Tb. N:+29. 4%,Tb. Sp:-28. 9%,均P＜ 0. 05). 8周去势组的小鼠在术后8周首次观察到BV/TV(-46. 1%,P＜ 0. 05),Tb. N(-52. 2%,P＜ 0. 05)及Tb. Sp(+57. 0%,P＜ 0. 05)较术前的显著性改变,上述参数的变化在随后的时间点有所减缓. 12周去势组小鼠则在去势6周后即可观察到上述参数的显著性变化(BV/TV:-26. 6%,Tb. N:-37. 1%,Tb. Sp:+59. 6%,均 P＜ 0. 05),并在随后的随访时间中进入平台期.结论 与DEXA相比,micro-CT更适合于评估小鼠模型的骨密度及骨微结构变化.本研究认为12 周是使用卵巢切除法建立雌性C57/BL6J成年小鼠绝经后骨质疏松模型的合适时机.%Objective To investigate the change of BMD and trabecular architecture in mature female C57/BL6J mice after ovariectomy( OVX), and to evaluate the appropriate timing of OVX to induce mice model of postmenopausal osteoporosis. Methods 60 mature female C57/BL6J mice were randomly divided into 8 w-OVX group and 12 w-OVX group. The mice in the former group were performed OVX at the age of 8 weeks while the rest mice were operated at the age of 12 weeks. DEXA was used for the assessment of BMD of total body, the spine, and the lower extremity. Micro-CT was used to measure the trabecular architecture and to reconstruct the 3D images of excised tibia at 0 day, 6 weeks, 8weeks, 10 weeks, and 12 weeks after the operation. Results There was no significant difference of BMD measured with DEXA between both groups at all the time points. Profound improvement of the bone structure was observed at 12 weeks comparing with that at 8 weeks (Tb. N:+29. 4%, Tb. Sp:-28. 9%, all P＜0. 05). Changes of BV/TV (-46. 1%, P＜0. 05), Tb. N (-52. 2%, P＜0. 05), and Tb. Sp (+57. 0%, P＜0. 05) in 8 w-OVX group didn’t reach statistical significance until 8 weeks after OVX, and reached a plateau thereafter. Those parameters changed significantly in 6 weeks after OVX in 12 w-OVX group (BV/TV;-26. 6%, Tb. N:-37. 1%, and Tb. Sp:+59. 6%, all P＜0. 05), and the change sustained in the next 6 weeks. Conclusion Micro-CT is more suitable for the evaluation of bone morphology and micro-architecture in mice models. OVX at 12 weeks is the appropriate timing to induce mice model of postmenopausal osteoporosis.