中国骨质疏松杂志

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

Ovariectomy on 12-week-old mature female C57/BL6J mice is the appropriate timing of animal model for postmenopausal osteoporosis

DOI：10.3969/j.issn.1006.7108.2018.05.005

中文关键词: 卵巢切除术骨质疏松症小鼠动物模型

英文关键词:Ovariectomy Osteoporosis Mice Animal model

基金项目:国家自然科学基金项目（81672186），广东省省科技厅省级科技项目（2014B020212004, 2014A020212134），中山大学孙逸仙纪念医院逸仙培育项目（2014）

作者

单位

傅光涛1 刘生2 李长川1 伍俊妍3 李仕勋1 秦岭4 刘伟1 邱俊雄1 彭芃1 丁悦1,5*

1. 中山大学孙逸仙纪念医院骨外科，广东广州 510120 2. 中山大学孙逸仙纪念医院核医学科，广东广州 510120 3. 中山大学孙逸仙纪念医院药学部，广东广州 510120 4. 香港中文大学医学院骨科&肌肉骨骼研究实验室香港 5. 中山大学孙逸仙纪念医院广东省恶性肿瘤表观遗传学与基因调控重点实验室，广东广州 510120

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中文摘要:

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（BV/TV: +23.7%，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。

英文摘要:

Objective To investigate the change of BMD and trabecular architecture in mature female C57/BL6J mice after 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 8w-OVX group and 12w-OVX group. The rats in the former group were performed OVX at the age of 8 weeks while the rest rats 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 (BV/TV: +23.7%, 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 8w-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 12w-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.

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