建立大鼠双膦酸盐相关颌骨骨坏死模型并初步分析其发病原因  

Establishment of bisphosphonate-related osteonecrosis of the jaw model in rats and preliminary analysis of its etiological mechanism

作　　者：马泽云[1] 王衣祥[2] 

机构地区：[1]北京大学口腔医学院.口腔医院特诊科,北京100081 [2]北京大学口腔医学院.口腔医院中心实验室,北京100081

出　　处：《北京大学学报（医学版）》2014年第6期945-949,共5页Journal of Peking University:Health Sciences

基　　金：首都卫生发展科研专项基金(2011-4025-02)资助~~

摘　　要：目的:建立大鼠双膦酸盐相关颌骨骨坏死(bisphosphonate-related osteonecrosis of the jaw,BRONJ)模型并初步分析其发病原因。方法:用帕米磷酸二钠、地塞米松加牙槽骨创伤(拔牙)的方法在大鼠体内建立了双膦酸盐相关颌骨骨坏死模型,并分析了CD4+和CD90+T淋巴细胞在双膦酸盐相关颌骨骨坏死发病过程中的变化。体外实验利用CCK-8法研究帕米磷酸二钠和地塞米松对人成骨肉瘤细胞MG-63和破骨前体细胞Raw 264.7的作用,初步分析双膦酸盐相关颌骨骨坏死的发病机制。结果:在牙槽骨创伤的前提下,成功地在帕米磷酸二钠和地塞米松联合用药组建立了大鼠BRONJ模型,流式细胞仪分析证实联合使用帕米磷酸二钠和地塞米松比单独应用这两种药物更能降低CD4+和CD90+T淋巴细胞在脾细胞中的比例。CCK-8实验证实帕米磷酸二钠能抑制MG-63及Raw264.7细胞的增殖,地塞米松能增强帕米磷酸二钠对抑制Raw 264.7细胞增殖的作用。结论:成功地建立了大鼠BRONJ模型,并证实了地塞米松可以增强双膦酸盐对破骨前体细胞抑制增殖作用;至少创伤、感染及地塞米松导致的免疫学反应等因素参与了BRONJ的发生和发展。Objective：To establish bisphosphonate-related osteonecrosis of the jaw （BRONJ） model in rats and to make preliminary analysis of its etiological mechanisms.Methods：A BRONJ model was established in rats using pamidronate,dexamethasone combined with alveolar bone trauma （tooth extraction） method,and the ratios of CD4 ＋ and CD90 ＋ lymphocytes in splenocytes were also analyzed by flow cytometry in each group.For in vitro studies,the effects of pamidronate and dexamethasone on the proliferation of human osteosarcoma cell line MG-63 and mouse pre-osteoclasts cell line Raw 264.7 were investigated using CCK-8 assay.Results：The rat BRONJ model was successfully established using the method described above.Flow cytometry results showed that the ratios of CD4 ＋ and CD90 ＋ lymphocytes in splenocytes were much lower in the pamidronate and dexamethasone-treated rats than those in either pamidronte alone-or dexamethasone alone-treated rats.CCK-8 assay results showed that pamidronate could inhibit the proliferation of both MG-63 and Raw 264.7 cell lines,while dexamethasone could enhance the inhibitory effect of pamidronate on Raw 264.7 cells.Conclusion：This study successfully established the BRONJ model in rats and verified that dexamethasone could enhance the inhibitory effect of pamidronate on pre-osteoclasts in vitro.At least three factors including alveolar bone trauma,infection and immune response induced by dexamethasone could be involved in the process of BRONJ.

关 键 词：双膦酸盐相关颌骨骨坏死 模型 动物 帕米磷酸二钠 地塞米松 免疫系统 

分 类 号：R364.26[医药卫生—病理学]