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唑来膦酸对小鼠下颌拔牙创早期修复过程的影响

Effect of zoledronic acid on mandibular socket healing process of mice at an early stage
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摘要 目的:通过构建小鼠双膦酸盐颌骨坏死(bisphosphonate-related osteonecrosis of the jaw,BRONJ)模型,探讨该类药物对拔牙创早期缺损修复过程的影响。方法:18只8~9周龄C57BL/6雄性小鼠,随机分为空白对照组及唑来磷酸给药组,通过腹腔注射+左下颌第一磨牙拔除诱导其产生双膦酸盐颌骨坏死样病变。随后选取术后3、5、7天3个时间点,H-E染色观察其大体愈合情况,Trap染色观察破骨细胞分布及数量,免疫组织化学染色观察早期成骨向转录因子及破骨特异性蛋白的表达差异。实验重复3次,采用ImageJ软件对图像进行分析和数据转换,采用SPSS 20.0软件包进行显著性分析。结果:与对照组相比,唑来膦酸给药组拔牙创早期缺损修复过程延迟。术后3天成骨转录因子RUNX2表达降低,术后7天破骨细胞特异性蛋白CTSK数量减少;术后早期TRAP表达降低,骨改建行为整体受到抑制。结论:唑来膦酸可在术后3天抑制成纤维细胞长入拔牙窝,并使RUNX2表达含量降低,抑制新骨形成。其还能使拔牙术后3、5、7天破骨细胞表达TRAP含量减少及在术后7天降低CTSK表达量,抑制破骨细胞行使骨吸收功能。 PURPOSE:To investigate how bisphosphonates affect early process of socket healing in mice model.METHODS:Eighteen 8-9 weeks C57BL/6 male mice were randomly divided into control and experimental group.Bisphosphonate-related osteonecrosis of the jaw(BRONJ)model was conducted by intraperitoneal injection of zoledronate(ZOL)and extraction of lower left first molar in mice.Three,five,seven day after surgery,the mice were sacrificed and paraffin-embedded slides were made.H-E staining was used to evaluate the gross condition.The distribution and amounts of osteoclasts were measured by TRAP staining.Finally,immunochemical staining was used to detect RUNX2 and CTSK level.All experiments were duplicated thrice,ImageJ was used for transformation of pictures and SPSS 20.0 software package was used for statistical analysis.RESULTS:In comparison with the control group,early process of socket healing in the experimental group was generally delayed.RUNX2,CTSK,TRAP expression level was decreased.On the whole,early bone remodeling process in ZOL injection group was suppressed.CONCLUSIONS:Zoledronic acid inhibited the migration of fibroblasts into socket,and reduced the expression of Runx2,hindering new bone formation.It also can reduce the expression of TRAP 3,5,7 days after tooth extraction and CTSK expression three days after operation,thus inhibiting the bone resorption function of osteoclasts.
作者 江润洋 康非吾 JIANG Run-yang;KANG Fei-wu(Department of Oral and Maxillofacial Surgery,School&Hospital of Stomatology,Tongji University,Shanghai Engineering Research Center of Tooth Restoration and Regeneration.Shanghai 200072,China)
出处 《上海口腔医学》 CAS 北大核心 2022年第4期349-353,共5页 Shanghai Journal of Stomatology
基金 国家自然科学基金(8167040476) 上海市科学技术委员会科研资助项目(16411961100)。
关键词 双膦酸盐性颌骨坏死 拔牙创修复 唑来膦酸 Bisphosphonate-related osteonecrosis of the jaws Socket healing Zoledronate
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