双膦酸盐致颌骨坏死的大鼠模型研究  

Study on the Pathogenesis of Bisphosphonate-related Osteonecrosis of the Jaw in Rats

作　　者：华洪飞 王宁涛[1] 张文杰[2] 张伟杰[1] 张志愿[1] 王绍义[1] 

机构地区：[1]上海市口腔医学重点实验室,上海交通大学医学院附属第九人民医院口腔颌面外科,上海200011 [2]上海市口腔医学重点实验室,上海交通大学医学院附属第九人民医院修复科,上海200011

出　　处：《口腔颌面外科杂志》2016年第1期19-24,共6页Journal of Oral and Maxillofacial Surgery

基　　金：国家自然科学基金(81271114)

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。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 extrac-tions of the left first superior molars under general anaesthesia, and were euthanized at 12 weeks postsurgery. After eutha-nizing 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 ex-posed 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 os-teocytic lacunae and heavily eroded surfaces）, around which were cancellous bones with a large number of lymphocytic in-filtration. 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.

关 键 词：颌骨坏死 动物模型 唑来膦酸 分子机制 

分 类 号：R782[医药卫生—口腔医学] R-332[医药卫生—临床医学]