摘要： 目的：建立稳定的双膦酸盐相关颌骨坏死大鼠模型，并初步探索其发病机制。方法：选取雌性SD大鼠20只，8周龄，随机分为实验组（15只），腹腔注射唑来膦酸溶液；对照组（5只），腹腔注射生理盐水。6周后分别拔除右侧上颌第一磨牙，术后12周取材，大体观察拔牙创愈合情况，将上颌骨行Micro CT和组织学检查。结果：实验组建立颌骨坏死模型12只，建模成功率为80%。实验组上切牙过度磨耗，牙冠短小，拔牙创处未见愈合，可见灰黄色死骨暴露；Micro CT显示拔牙创处牙槽骨缺损，组织学显示拔牙创周围死骨形成，骨陷窝呈空泡状，死骨周围骨组织内有较多淋巴细胞浸润，牙周膜纤维疏松紊乱，牙髓腔可见血管扩张。免疫组化示骨坏死区域VEGF表达明显降低。结论：本实验成功建立双膦酸盐颌骨坏死大鼠模型，初步探讨其发病机制可能与局部慢性炎症以及VEGF表达异常等相关。

关键词: 颌骨坏死；  , 动物模型；  , 唑来膦酸；  , 分子机制

Abstract:  Objective： To establish a reliable model of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in rats and study the mechanism of pathogenesis. Methods: 20 female sprague-dawley rats aged 8 weeks were randomly divided into two groups. An experimental model of BRONJ was induced [zoledronic acid (ZA); every other day; n=15] and a matched void  controls [saline solution (CTL); n=5]. After 6 weeks of drug treatment, all animals were subjected to extractions of the left first superior molars under general anaesthesia, and were euthanized at 12 weeks postsurgery. After euthanizing all the rats, except for the descriptive evaluation, properties of the target sites were assessed by Micro-computed tomography (Micro-CT) and histopathology examination. Results: The osteonecrosis rate of survived rats was 80%(12/15). By clinical examination, the excessive attrition of the upper incisors, in the ZA group, as well as the significant areas of exposed bone necrosis were seen as compared to the CTL group. The Micro-CT scanning demonstrated significant bone defect on the alveolar socket of the ZA group. Histological sections of these lesions showed areas of bone necrosis (empty osteocytic lacunae and heavily eroded surfaces), around which were cancellous bones with a large number of lymphocytic infiltration. The arrangement of the periodontal ligament were loose and disordered; blood vessel dilation could be observed in ZA group. Immunohistochemical findings indicated that the local VEGF expression of the bone necrosis was obviously lower. Conclusions: A stable model of BRONJ can be induced, indicating that it may have something to do with the chronic inflammation and the abnormity of VEGF expression in the pathogenesis of BRONJ.

Key words:  osteonecrosis of the jaw, animal models, zoledronic acid, molecular mechanisms

中图分类号: 

• R782.13