重组人骨形态发生蛋白2局部注射促进兔胫骨延长区的骨愈合

Percutaneous injection of recombinant human bone morphogenetic protein 2 accelerates rabbit tibia union after distraction

目的:骨形态发生蛋白与骨延长关系的报道很少。为观察其对于牵拉骨再生延长区骨愈合的作用,将重组人骨形态发生蛋白2经皮注射到兔胫骨延长区,行组织学验证。方法:实验于2004-06/2005-03在吉林大学基础医学院实验动物中心完成。①实验材料:雄性日本大耳白兔30只;重组人骨形态发生蛋白2(由美国哈佛医学院分子骨科中心Oliver博士馈赠)。②实验干预及分组:制作日本大耳白兔延长区骨再生不良动物模型24只,行快速延长,2次/d,1mm/次,2mm/d,共延长10d,共2cm。将兔子随机分为2组,每组12只。对照组,延长结束后延长区注射醋酸盐缓冲液;重组人骨形态发生蛋白2组,延长结束后延长区注射醋酸盐缓冲液溶解的重组人骨形态发生蛋白2。③实验评估:延长结束后2周、4周时2组各取4只兔,麻醉后处死,进行延长区拍摄X射线片及延长区骨标本组织学光镜检查。结果:术中兔死亡及针道处骨折6只,24只进入结果分析。①延长区X射线片评价:延长结束后2周和4周时,显示重组人骨形态发生蛋白2组新生骨痂明显多于对照组,延长结束后4周时重组人骨形态发生蛋白2组髓腔开始形成。②延长区组织学观察结果:延长结束后4周时,对照组延长区周新生软骨、骨增多,融合成片,出现编织骨。重组人骨形态发生蛋白2延长区软骨细胞吸收矿化,转化为编织骨,并逐渐向皮质骨改建塑形。结论:牵拉骨再生延长结束后,延长区经皮注射重组人骨形态发生蛋白2,经间接X射线及组织学直接验证,对延长区骨愈合有促进作用。

AIM： There are few reports about the correlation between bone morphogenetic protein and bone lengthening. In this study, we observe the effect of recombinant human bone morphogenetic protein 2 （rhBMP2） on the consolidation phase of distraction osteogenesis in a rabbit model of leg lengthening. METHODS： The experiment was conducted in the experimental animal center of Basic Medical College of Jilin University from June 2004 to March 2005. Twenty-four of 30 male Japan White Rabbits were selected to make models of tibial lengthening with external fixator. The tibiae were distracted twice daily, 1 mm once, 2 mm daily for 10 days and 2 cm. Then the animals were randomly divided into two groups with 12 rabbits in each group： In control group, the animals were peroutaneously injected with acetate buffer solution into the lengthened area; rhBMP2 group was injected with rhBMP2 （given by Dr. Oliver, Orthopedic Center, Harvard Medical School）. Four rabbits of each group were selected respectively at 2 and 4 weeks after distraction and executed under anesthesia. The lengthened area was given X-ray and light microscope examination. RESULTS： Six rabbits died or suffered fracture during operation, finally 24 ones were involved in the result analysis. ① Radiographic evaluation indicated that there was a significant increase in bony union of the distraction area in rhBMP2 group compared with the control group at 2 and 4 weeks. At 4 weeks after distraction, medullary cavity was formed in rhBMP2 group. ②Light microscope evaluation showed that there were new cartilage around lengthened area, and the bone fused into sheet, and woven bone was found in control group; in rhBMP2 group, the chondrocytes in lengthened area were mineralized and transformed into woven bone, and gradually transferred into os integumentale. CONCLUSION： X-ray and histological examination have proved that injection of rhBMP2 at the end of lengthening period significantly enhances the consolidation stage of distraction osteogenesis in the rabbit model.