节点文献
骨生长因子对牵张成骨的作用
The Effect of Bone Growth Factors on Distraction Osteogenesis
【作者】 王战鑫;
【导师】 徐勇忠;
【作者基本信息】 吉林大学 , 口腔临床医学, 2006, 博士
【摘要】 牵张成骨技术已经在临床应用几十年,以其独有的成骨方式和其他技术无可比拟的临床效果,一直备受医学界的青睐。近年来,随着牵张器不断在改进,手术设计的不断完善,该技术得到了突飞猛进的发展,在临床应用的范围也越来越广。但是牵张成骨技术也同样存在不足,如病程长,骨形成不良等。本课题的研究目的是寻找加速牵张成骨的方法,以缩短疗程。 首先,本文应用自主开发研制的外置式牵张器,以兔为实验对象,建立了牵张成骨的动物实验模型;然后通过免疫组化技术和Northern Blot技术对BMP-2和FGF-β1在兔下颌牵张成骨过程中的表达及意义进行阐述;最后利用外源性的BMP-2和TGF-β1促进牵张成骨过程中新骨生成和钙化。 本实验发现,家兔可作为牵张成骨实验理想的实验动物。我们研制的兔下颌骨外置式牵张器,设计合理,经济实用,是理想的实验器材。其次,BMP-2和TGF-β1在牵张期都有高度表达,到固定期开始减弱,二者在表达上存在时间的一致性。最后,发现单独应用BMP-2可以加速成骨,而TGF-β1对牵张成骨没有促进作用。但二者联合应用可发挥协同作用。 本文的主要成果是开发了一种实验用外置式兔下颌骨牵张器,探讨了BMP-2和TGF-β1在兔下颌牵张成骨过程中的表达规律,并找到了一种利用骨生长因子促进牵张成骨的方法,这为今后该技术的基础研究和临床应用提供一定的理论依据。
【Abstract】 Distraction osteogenesis (DO) is a new technique for correction of the congenital craniofacial deformity and acquired bone defect. Comparing to the conventional orthognathic surgery techniques, DO is less invasive and no need for bone grafting. In addition, soft tissue simultaneous expansion may improve long-term stability. But there are still some defects, including long duration of treatment and complications of local infection and bone ununion of distraction gap. Therefore, the key problem of clinical work is to accelerate osteogenesis and shorten the course treatment. The experiment studied the expression of endogenous bone growth factors (BMP-2& TGF- β1) during mandibular lengthening and the effects of exogenous bone growth factors on distraction osteogenesis by the model of mandibular distraction osteogenesis in rabbits. The purpose is that the experiment provides bases to find an effective measure to accelerate bone regeneration during mandibular lengthening.In our study, we established an animal model for lengthening the mandibular by DO in rabbits. The new generation bone were studied by X ray and histology research. To study the expression of BMP-2 and TGF- β1 during the different stage on DO, we used immuno- -histochemistry and molecular biology technique. In addition, we studied the effect of BMP-2 and TGF- β1 on DO by X ray , SEM examination and bone histomorphometry. The main content is to discuss the effect of exogenous bone growth factors on new bone formation and the relationship of BMP-2 and TGF- β1 during the course of DO.The results show.1. The model of mandibular distraction osteogenesis in rabbits is created successfully.2. The positive expression of bone growth factors in distraction zone is observed during mandibular lengthening. Different bone growth factors express different intensities in different parts.3. Positive staining for BMP-2 was mainly observed in the mesenchymal cells and the active osteoblasts at the edge of new born trabecular bone. Their strongest expression was noted at 0th day after distraction. At the 28th day after distraction, only weak BMP-2 expression was detected in those cells.4. Staining for TGF- P i was localized in mesenchymal cells and osteoblasts, on 0th day after distraction, a marked increase in TGF- £ i expression was observed in the regenerated bone. On the 28th day, TGF- P i showed weak staining.5. The bone regeneration in group A was superior to that of group B and C after DO at the rate of lmm/d. There were no marked differences between group B andC.6. At the rate of 2mm/d , the new bone formation of group A and group C were superior to that of group B and D. Group C was superior to group A, and group B and D were no new bone formation at the rate of 3mm/d.As follow of the conclusion:1. BMP-2 and TGF- £ i appear to play an important role in bone regeneration after DO.2. Exogeneous BMP-2 can accelerate bone formation during DO in rabbits.3. Exogeneous TGF-13 j may have no beneficial effect on bone regeneration following mandibular osteodistraction in rabbits.4. There is a synergetic action between BMP-2 and TGF- P i on DO. Using the two bone growth factors at the same time is better than using one of them for new bone formation on DO.
【Key words】 distraction osteogenesis; BMP-2; TGF-β1; new bone formation;