骨膜蛋白促进兔下颌骨快速牵张成骨的实验研究

Experimental study of periostin promoting rapid distraction osteogenesis of the rabbit mandible

目的探讨骨膜蛋白对兔下颌骨快速牵张成骨的促进作用,为临床应用提供实验依据。方法 24只新西兰雄性白兔行牵张成骨手术后,经过3 d的滞留期,以2 mm/d(共计5 d)牵张速率进行快速牵张,随后实验动物被随机分为A组和B组(每组12只)。牵张结束当天开始每天牵张间隙注射含40μg重组骨膜蛋白的0.5 mL生理盐水(B组)或等体积生理盐水为对照组(A组)共8 d。牵张结束后4周和8周,每组随机抽出8只样本全麻下进行CT扫描,应用双能X线吸收法检测骨矿密度和骨矿含量。牵张结束后8周,全部实验动物被处死,每组随机选取6只样本进行micro-CT和组织学检查,剩余样本进行生物力学测试。结果 CT影像提示在牵张结束后4周及8周B组动物牵张间隙新骨生成明显优于A组。在牵张结束后4周及8周B组牵张间隙骨矿密度分别是(0.157±0.016)g/cm^2和(0.234±0.023)g/cm^2,而骨矿含量分别为(0.096±0.010)g及(0.204±0.017)g,均明显高于A组(P <0.001)。micro-CT图像及数据提示B组牵张间隙显微结构具有更成熟特征。组织学实验提示B组牵张间隙骨小梁粗大、成熟,软骨细胞少。生物力学测试结果 B组牵张间隙生物力学强度为(228.47±39.98)N,为A组的1.24倍(P=0.045)。结论在兔下颌骨牵张间隙间断使用骨膜蛋白能促进局部新骨生成和矿化。

Objective To explore the promoting effect of periostin on rapid distraction osteogenesis of the rabbit mandible and provide experimental evidence for the clinical use of periostin to promote osteogenesis. Methods Twenty-four New Zealand male white rabbits underwent distraction osteogenesis, and after 3 days of retention, they were rapidly stretched at a stretch rate of 2 mm/d(total 5 d). The animals were randomly divided into group A and group B(12 per group). On the last day of the stretch, 0.5 mL of normal saline containing 40 μg of recombinant periostin was given to group B or an equal volume of normal saline was added to the control group(group A) for 8 days. At 4 weeks and 8 weeks post-stretch, 8 animals were randomly selected from each group to undergo a CT scan under general anesthesia.The bone mineral density and bone mineral content were detected by dual energy X-ray absorptiometry. Eight weeks post-stretch, all of the experimental animals were sacrificed. Six animals were randomly selected from each group for micro-CT and a histological examination, and the remaining animals were subjected to biomechanical tests. Results CT images showed that the new bone formation in the distraction space of group B was significantly better than that of group A at 4 and 8 weeks post-stretch. At 4 weeks and 8 weeks post-stretch, the bone mineral density in group B was(0.157 ± 0.016) g/cm^2 and(0.234 ± 0.023) g/cm^2, respectively, and the bone mineral content was(0.096 ± 0.010) g and(0.204 ± 0.017) g, respectively. The above four means were significantly higher in group B than in group A(P 0.001).The micro-CT images and data suggest that the stretch gap microstructure of group B has more mature features. Histological experiments showed that the trabecular bone of group B was thick and mature, with few chondrocytes. The biomechanical test results showed that the biomechanical strength of the distraction gap in group B was(228.47 ± 39.98) N,which was 1.24 times that of group A(P = 0.045). Conclusion Interstitial use of periosteal protein in the distraction space of the mandible in rabbits can promote local new bone formation and mineralization.