唑来膦酸对大鼠不同胚胎来源骨骼Dlx-5和Msx-1表达的影响

The effect of zoledronate on the expression of Dlx-5 and Msx-1 in different bones of rats

目的:探讨唑来膦酸对远中缺失同源盒基因5(Distal-Less homeobox 5,Dlx-5)和肌节同源盒基因1(Msh homeobox 1,Msx-1)在大鼠下颌骨和髂骨表达水平的影响,以期为进一步研究双膦酸盐类药物导致颌骨骨坏死的致病机制提供理论基础。方法:选用24只8周龄雌性SD大鼠,实验组腹腔注射唑来膦酸持续12周,对照组腹腔注射等量生理盐水12周,采集下颌骨以及髂骨样本,应用免疫组化及RT-PCR检测大鼠上述两个部位Dlx-5和Msx-1在蛋白水平和基因水平的表达情况。结果:免疫组化及RT-PCR结果显示实验组中下颌骨Dlx-5的蛋白和基因表达水平均高于对照组(P<0.01),髂骨Dlx-5的蛋白和基因表达水平低于对照组(P<0.05),实验组中下颌骨和髂骨Msx-1的蛋白和基因表达水平均低于对照组(P<0.01)。对照组中与髂骨比较,下颌骨的Dlx-5基因表达水平降低(P<0.01),下颌骨的Msx-1基因表达水平升高(P<0.01)。结论:在唑来膦酸作用下,大鼠下颌骨和髂骨Dlx-5和Msx-1的表达水平存在差异性变化。在一定程度上解释了双膦酸盐类药物导致颌骨骨坏死特异性发生于颌骨的原因。

Objective：To investigate the effects of zoledronate on expression of Dlx-5 and Msx-1 in mandible and ilium of rats for a future study of pathogenesis of bisphosphonate-related osteonecrosis of the jaw. Methods：Twenty four 8 wk old female Sprague-Dawley rats were selected in this study. The rats of the experimental group（n=12） were injected intraperitoneally with zoledronic acid for 12 weeks, and those of the control group（n=12） were injected intraperitoneally with same amount of normal saline for 12 weeks. We use immunohistochemistry and reverse transcriptase-polymerase chain reaction（RT-PCR） to examine expression levels of Dlx-5 and Msx-1 in mandible and ilium samples. Results：The results of immunohistochemistry and RT-PCR showed that the expression of Dlx-5 at protein and gene level in mandible was increased in the experimental group compared with the control group（P〈0.01）. The expression of Dlx-5 at protein and gene level in ilium was decreased compared with the control group（P〈0.05）. The expression of Msx-1 at protein and gene level in mandible and ilium was decreased in the experimental group compared with the control group（P〈0.01）. In the control group, expression level of Dlx-5 in mandible was decreased compared with ilium（P〈0.01）. In the control group, expression level of Msx-1 in mandible was increased compared with ilium（P〈0.01）. Conclusions：With treatment of zoledronate,there were site-specific differences of the altered tendency of Dlx-5 and Msx-1 expression in mandible and ilium of rats,indicating a certain restriction of bisphosphonate-related osteonecrosis to jaw bones.