远中缺失同源盒基因5和肌节同源盒基因1在双膦酸盐药物性颌骨坏死大鼠模型中的变化

Changes of distal-less homeobox genes 5 and Msh homeobox 1 in a rat model of bisphosphonate related osteonecrosis of the jaw

目的探究远中缺失同源盒基因5（distal-less homeobox genes 5，Dlx-5）和肌节同源盒基因1（Msh homeobox 1，Msx-1）在双膦酸盐药物性颌骨坏死（bisphosphonate-associated osteonecrosis of the jaw，BRONJ）致病机制中的作用。方法将24只SD大鼠采用随机数字表法随机分为两组，每组12只。实验组腹腔注射唑来膦酸0.2 mg/kg，对照组腹腔注射等量生理盐水，每周3次，12周后拔除左下第一磨牙。拔牙后8周处死所有动物。通过影像学、大体及组织病理学观察，诊断BRONJ的发生。通过实时荧光PCR检测Dlx-5和Msx-1在骨坏死样本中的表达水平。结果BRONJ动物模型中，实验组Dlx-5基因表达（5.91±0.28）显著高于对照组（1.00±0.15）（t=15.778，P=0.001），实验组Msx-1基因表达（0.09±0.03）显著低于对照组（1.02±0.06）（t=-10.638，P=0.001）。结论腹腔注射唑来膦酸联合拔牙的方法可成功诱导大鼠发生BRONJ，Dlx-5和Msx-1基因在BRONJ的致病过程中发挥作用。

ObjectiveTo further study the effects of distal-less homeobox gene 5 （Dlx-5） and Msh homeobox 1 （Msx-1） in the pathogenic mechanism of bisphosphonate related osteonecrosis of the jaw （BRONJ） .MethodsTwenty-four SD rats were divided into two groups, the experimental group was injected intraperitoneally with zoledronic acid for 12 weeks （0.2 mg/kg, three times a week）, and the control group was injected with saline solution for 12 weeks. The first mandibular molars were extracted after 12 weeks. All of the animals were sacrificed eight weeks after teeth extraction. The BRONJ was diagnosed by gross observation, X-ray examination and histopathlolgical examination. Through real-time PCR, the expression level of Dlx-5 and Msx-1 were detected in the mandible of BRONJ samples and normal samples.ResultsX-ray examination and histopathlolgical analysis showed the presence of BRONJ. The results of real-time PCR showed that the expression levels of Dlx-5 were increased （P=0.001） and the expression level of Msx-1 was decreased （P=0.001） in the experimental group compared with the control group.ConclusionsDlx-5 and Msx-1 genes play roles in the pathogenic mechanism of BRONJ.