摘要
目的研究沙利度胺对双膦酸盐相关颌骨坏死的影响。方法 36只大鼠随机分成A、B、C组,分别接受生理盐水、唑来膦酸、唑来膦酸+沙利度胺治疗。用药3周后,拔除大鼠左上颌第1磨牙。拔牙后4、8周,收获标本,评价颌骨坏死、微血管生成及细胞凋亡情况。结果拔牙后4、8周,大鼠上颌骨拔牙创处均无死骨裸露,但B组、C组部分标本可见一些小的瘘管。组织学检查显示,A组标本未见死骨,而B组、C组在拔牙窝周围可见小块死骨。B组、C组拔牙窝周围区域空骨陷窝百分比和死骨面积显著多于A组(P<0.01),而骨陷窝密度则显著下降。B组、C组微血管密度较A组也显著降低,在4周时分别下降了和25.87%和55.27%(P<0.01),在8周时分别下降了45.62%和72.84%(P<0.01);凋亡细胞数则在4周时分别增长了54.80%和87.89%(P<0.01),在8周分别增长了208.08%和250.58%(P<0.01)。结论沙利度胺加重了唑来膦酸诱发的早期阶段的颌骨坏死;沙利度胺和唑来膦酸对颌骨坏死的作用与微血管生成抑制有关。
Objective To investigate the effect of thalidomide on the development of bisphosphonate-related osteonecrosis of the jaws （BRONJ）. Methods Thirty-six rats were randomly divided into groups A, B and C, and treated with saline, zoledronate and zoledronate plus thalidomide, respectively. Three weeks later, the left maxillary first molars of the rats were extracted. Four and eight weeks after tooth extraction, samples were harvested for evaluation of osteonecrosis of the jaws, microvessel density, and cell apoptosis. Results At both of the time points, no exposed dead bone was observed at the extraction socket areas in the rats except for some small fistulas in groups B and C. Histological examination confirmed the absence of dead bone in group A, whereas small areas of dead bone were observed around the extraction socket in groups B and C. Compared with those in group A, the percentage of empty lacunae and the area of dead bone were significantly increased （P〈0.01）, whereas bone lacunae density was significantly decreased （P〈O.01） in groups B and C at both time points. Microvessel density in groups B and C were also significantly decreased （P〈0.01） by 25.87% and 55.27% at week 4, and by 45.62% and 72.84% at week 8, respectively; the apoptotic cells in groups B and C increased by 54.80% and 87.89% at week 4 （P〈0.01）, and by 208.08% and 250.58% at week 8 （P〈0.01）, respectively. Conclusion Thalidomide can aggravate zoledronate-induced early-stage BRONJ, and their osteonecrosis-inducing effect of the jaw may be attributed, at least partly to the inhibition of angiogenesis.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2015年第8期1084-1089,共6页
Journal of Southern Medical University
基金
国家自然科学基金(81270965
81101448)
河北省自然科学基金(C2011401044)~~
