骨缝牵引中联合应用骨形态发生蛋白-2和骨保护素的实验研究

The effect of bone morphogenetic protein-2 and osteoprotegerin in trans-sutural distraction osteogenesis

目的探索上颌骨在骨缝牵引时加入缓释骨形态发生蛋白-2(BMP-2)和骨保护素(OPG)对新骨形成的影响。方法以24只杂种犬为研究对象,随机分为A、B、C组。通过手术在上颌骨腭横缝植入自制的新型牵引器。A、C组术后5 d在牵引区附近注射缓释重组人骨形态发生蛋白-2/聚乳酸-羟基乙酸共聚物/纤维蛋白胶(rhBMP-2/PLGA/FS),B、C组在牵引3周后注射人骨保护素/纤维蛋白胶(rhOPG/FS)。牵引1、2、4、6周后处死动物,采集标本进行组织学染色,并通过组织计量学方法检测腭横缝的组织改建情况。结果A、C组骨缝区成骨细胞功能活跃,透射电镜显示细胞内有大量高尔基复合体、线粒体及粗面内质网。牵引6周时,A、B、C组成骨细胞指数分别为38.5±7.7、35.7±6.5、41.7±11.0,破骨细胞指数分别为5.9±1.0、1.2±0.3、2.8±0.4,骨小梁厚度分别为(38.36±13.28)、(66.20±9.16)、(51.85±9.92)μm;B、C组表现出骨密度增加及破骨细胞指数下降。结论本实验所用牵引器能促进新骨生成;BMP-2与OPG在骨缝牵引过程中有协同作用,可以促进新骨形成及骨改建。

Objective To determine if locally administered bone morphogenetic protein-2（BMP-2） and osteoprotegerin（OPG） improved osteogenesis and new bone formation by trans-sutural distraction osteogenesis.Methods Twenty four dogs were divided into three groups randomly and received new internal trans-sutural distraction osteogenesis treat-ment.Five days after operation,infusion apparatus with double-tube was inserted to submucosa near the distracted zone to deliver controlled release agent of recombinant human bone morphogenetic protein-2/poly（lactic-co-glycolic acid）/ fibrin sealant（rhBMP-2/PLGA/FS） in group A and group C.Recombinant human osteoprotegerin/fibrin sealant（rhOPG/ FS） was injected three weeks later in group B and group C.Histology staining and bone histomorphometry were used to measure the changes of maxillary bone sutura after distraction for 1,2,4 and 6 weeks.Results New bone formation observed in distracted zone showed a significant increase in group A and C.Transmission electron microscope showed the osteoblast and osteocyte were active with dilated rough endoplasmic reticulum and a large number of chondriosomes and Golgi complex.After distraction for 6 weeks,indexes of osteoblast of group A,B,and C were 38.5±7.7,35.7±6.5,and 41.7±11.0,indexes of osteoclast（Ioc） were 5.9±1.0,1.2±0.3,and 2.8±0.4,bone trabecula thicknesses were（38.36± 13.28）,（66.20±9.16）,and（51.85±9.92） μm respectively.Increased bone density and decreased Ioc were found in group B and C.Conclusion The new elastic distractor is effective in inducing new bone formation.BMP-2 and OPG com-bination acts synergistically,and leads to significant enhancement of bone formation and remodeling.