特立帕肽对大鼠药物相关性颌骨坏死模型作用的实验研究

Experimental study of the effect of teriparatide on a medication-related rat model of osteonecrosis of the jaw

目的:建立稳定的药物相关性颌骨坏死(medication-related osteonecrosis of the jaw,MRONJ)模型,探究特立帕肽对MRONJ的治疗作用。方法:选择10月龄SD大鼠,经尾静脉注射唑来膦酸(80μg/kg),每周1次,持续7周,第8周拔除右上颌第一、第二磨牙。拔牙术后8周,观察大鼠颌骨坏死情况。将颌骨坏死建模成功的动物随机分为对照组和实验组,分别接受生理盐水和特立帕肽(60μg/kg,每周3次)皮下注射治疗,4周后处死大鼠,进行大体观察、组织学检测、micro-CT检测,评价特立帕肽对MRONJ的治疗效果。结果:对照组大鼠颌骨坏死未见愈合,且坏死程度加重;micro-CT影像见颌骨纹理紊乱,边缘粗糙,死骨形成,骨破坏区与鼻旁窦相通。实验组见大鼠拔牙创逐渐缩小,67%的大鼠拔牙创完全愈合;micro-CT影像见拔牙创内新骨形成,牙槽骨愈合征象。结论:特立帕肽对大鼠MRONJ具有显著的治疗作用。

Objective:To establish a stable model of medication-related osteonecrosis of the jaw(MRONJ),and to explore the therapeutic effect of teriparatide on MRONJ.Methods:10-month-old SD rats were selected and injected with zoledronic acid(80μg/kg)via tail vein once a week for 7 weeks;the first and second molars of the right maxillary were extracted in the 8th week.Eight weeks after tooth extraction,the rat jaw osteonecrosis was observed.The animals with successful modeling of osteonecrosis of the jaw were randomly divided into the control group and the experimental group,and received subcutaneous injection of saline and teriparatide(60μg/kg,3 times a week),respectively.The animals were sacrificed 4 weeks later.Histology and micro-CT analysis were performed to evaluate the therapeutic effect of teriparatide on MRONJ.Results:In the control group,the rat jaw osteonecrosis did not heal,and the degree of necrosis was aggravated.Micro-CT images showed disordered jaw texture,rough margins,and sequestrum formation.The bone destruction area communicated with the paranasal sinus.In the experimental group,the extraction wounds were gradually reduced,and 67% of the extraction wounds in the rats were completely healed;micro-CT images showed new bone formation in the extraction wound and the signs of alveolar bone healing.Conclusion:Teriparatide has a significant therapeutic effect on MRONJ in rats.