局部激活破骨细胞对大鼠应用双膦酸盐后拔牙创愈合的影响

Influence of Local Osteoclast Activation on the Healing of Tooth Extraction Wound under Bisphosphonates Administration

目的:通过动物模型,研究局部激活破骨细胞对应用双膦酸盐后拔牙创愈合的影响,以期找到预防双膦酸盐相关性颌骨坏死的方法。方法:选用24只8周龄雌性SD大鼠随机分为实验组和对照组,行双侧卵巢切除术(ovariectomy ,OVX),术后3个月开始应用双膦酸盐。用药一个月后,拔除大鼠左侧上颌第一磨牙。实验组拔牙创内放置含有巨噬细胞集落刺激因子(macrophage-colony stimulating factor, M-CSF)与核因子-κB受体活化因子配体(the receptor activator of nuclear factor-κB ligand, Rankl)的明胶海绵,对照组放置含有生理盐水的明胶海绵。拔牙后2周,收取样本,评价拔牙创愈合情况。结果:TRAP染色结果显示实验组牙槽窝内的破骨细胞数量较对照组明显增多。免疫组织化学染色结果显示实验组成骨能力标记物骨桥蛋白(osteopontin,OPN)、牙本质基质蛋白1(dentin matrix protein 1,DMP1)表达量增加。组织学检测结果显示实验组拔牙创牙槽窝新生骨质较对照组明显增多。结论:局部激活破骨细胞可以促进应用双膦酸盐后的拔牙创愈合。

Objective: The aim of this study is to explore the influence of local osteoclast activation during bisphosphonate administration on the healing of tooth extraction wound. Methods: 24 female SD rats at the age of 8-weeks were divided into experimental group and control group randomly. The first maxillary molar was extracted after 3 months of ovariectomy which followed by zoledronic acid treatment for 1 month. Gelfoam with Rankl (the receptor activator of nuclear factor-κB ligand) and M-CSF (macrophage-colony stimulating factor, M-CSF) was placed in tooth extracted socket in experimental group while gelfoam with saline for control group. The animals were sacrificed to evaluate wound healing of tooth extraction after 2 weeks. Results: Wound healing in the experimental group was better than that in the control group. The histological staining displayed more osteogenesis in the experimental group followed by increased number of osteoclast showed by TRAP staining. Immunohistochemical staining revealed a stronger bone formation ability(opn and dmp1) in experimental group. Conclusion: Activated osteoclasts can promote the healing of tooth extracted socket after the application of bisphosphonates.