下颌皮质骨颊向牵张成骨的实验研究
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摘要
口腔颌面部先天性和获得性畸形与缺损，特别是下颌骨畸形在临床是比较常见的，多为发育畸形或肿瘤术后、外伤和炎症所引起，造成病员外貌畸形及功能障碍。对于这一类疾病，以往的治疗方法是采用正颌外科或植骨的手段，常常都需要另开辟手术区取骨，给患者带来痛苦。自1992年McCarthy最先成功利用口外牵引治疗颜面发育不足中下颌骨畸形以来，牵张成骨(Distraction Osteogenesis DO)已经逐渐成为矫治牙颌面发育不足及整复颌骨畸形的一个重要手段。它的最大优点是不需额外取骨来治疗某些颌骨缺损或畸形，减小了手术创伤。
近年来，国内学者在近远中向及垂直向牵张进行了大量动物实验和临床研究，并已将牵张成骨用于治疗颌骨缺损、小颌畸形、阻塞性呼吸睡眠暂停综合征、腭裂等临床病例，疗效是确切的。本实验在复习文献的基础上，设计了犬下颌骨颊向牵张成骨机理的研究课题，旨在探讨下颌骨颊舌向牵张的可行性，为三维牵张提供一定的实验基础。
本实验将12只犬下颌骨左侧单皮质骨方块截骨，安置半埋置型牵张器，延迟7天后，以2次/天，0.5mm/次的速度向颊侧牵引，延长7天后固定，右侧截骨后不牵引做为对照。分别在固定后第4天、第1、2、4、6、8周等时段取材，多聚甲醛固定。脱钙后行常规HE及改良Mallory's三色法染色，结果示左侧牵张区明显向颊侧隆起7mm，牵张区有大量新骨形成，至8周时钙化良好，x线显示与周围正常骨相连续。而对照组则
第四军医大学硕士学位论文
为正常骨折愈合过程。
另取材不脱钙，行成骨组织扫描电镜观察和二线能谱分析钙磷元素
含量变化。结果发现随牵张后固定时间的延长，各实验组钙、磷元素含
量逐渐增高，新骨组织是向着正常骨组织质和量的方向进行矿化，钙磷元
素参与了骨质矿化的全过程。
牵张成骨中有很多生长因于参与，本实验观察了各个时段整合素el
在新骨成骨细胞和破骨细胞上的表达，发现其在不同时段的表达水平不
同。成骨细胞膜上整合素pl在牵张后第一周开始表达，第2－4周表达最
强，第8周恢复正常水平。破骨细胞在第4天弱阳性表达，一周后明显抑
制，第4周基本消失。初步论证其可能介导了牵张中机械应力信号转导。
有关其与其它信号分子间的相互作用以及对其介导的细胞内应力信号
（第二信号通道）传递有待作进一步的研究。
总之，本课题的实验结果表明下颌骨颊舌向牵张成骨是可行的，其
组织学变化与前后向、垂直向牵张相似。扫描电镜及能谱分析提示颊舌
向牵张过程符合DO基本原则，固定至4－6周可考虑拆除牵张器，至8周时
可行使正常生理功能。CI、P元素参与了牵张的整个过程。整合素el可
能介导了机械应力转导，将机械信号转化为成骨信号。以上结果为临床
颊向牵张治疗偏面小颌畸形提供了有效的实验依据。
The congenital or acquired deformity and defect, esp the deformity of mandible, is common in clinic. Most of them were caused by postoperation, trauma and inflammation, leading to dysfunction and physiognomy malformation. From 1992, McCarthy firstly introduced the use of extraoral distractor to treat deformity of mandible, distraction osteogenesis became an important method to correct oral and maxillofacial underdevelopment and formities of facial skeleton.
Many animal experiments and clinic cases have been reported to investigate the medial-distal and vertical distraction in recent years. Such as dysostosis, defect of mandible,micrognathia,OSAS,palate cleft and so on.At the bottom of many reviews, this study designed bucco-lingular distraction of canine's mandible,in order to inquiry the possibility of bucco-lingular distraction.Also,the study might supply a experimental basis of three-dimensional distraction.
In this experiment, a half-buried distractor has been used after the square osteotomy to unilateral cortical bone of twelve canine's bilateral mandible. The bone segment of left mandible was elongated buccally after a consolidation phase of 7 days. The distraction protocol consisted of a rate of 0.5mm twice daily for 7 days, while right bone segment didn't proceed
distraction as control. The new osteogenesis were obtained and decalcified and paraffin slices were made respectively on the 4th day, the 1st, 2nd, 4th, 6th, 8th week after distraction complete. The slices were stained with HE and modified Mallory's. The results indicated that the left distraction segment obviously eminence buccally. The newly generated bone could be observed in distraction gap and it calcificate well at 8th week. The newly bone were continuous with circumference normal bone.
Other specimens didn't decalcify and processed for SEM evaluation and Ca/P ratio assay.With elongation time of the consolidation,the contents of Ca, P bundle were found to be elevated in the experiment. The newly generated bone decalcified as well as nomal bone with the maturity of distracted callus. It also shows that Ca, P element took part in the whole procedure of bone generation.
Many growth factors have been proved to produce a marked effect on
DO. In this study, The expression of integrin β1 in bone tissue, especially in the membrane of osteoblast and osteoclast was detected differently. In
osteoblasts, integrin β1 expressed increased on the 1 st week, maximum on the 2nd~4th week and normal on the 8th week. In osteoclast, inferior positive expression of integrin β1 was observed on the 4th day, decreased on the 1 st week and disappeared on the 4th week.The increased expression of integrin β 1 in osteoblast suggested that integrin β1 has a critical influence on distraction osteogenesis, and likely relates to the mechanical signal transduction. The interaction of the integrin and other signal molecul and the strain delivering from inter-cells should be studied further and deeply in future.
In general, the experiments in this study showed that bucco-lingular
distraction is feasible and coincident with the principle of DO by XRS. The Ca, P element had been proved to participate the whole distraction. Integrin β1 probably took part in transducting the mechanical signal to osteogenesis's signal.The results of the study might provide effective basis on treating HFM in clinic.
近年来，国内学者在近远中向及垂直向牵张进行了大量动物实验和临床研究，并已将牵张成骨用于治疗颌骨缺损、小颌畸形、阻塞性呼吸睡眠暂停综合征、腭裂等临床病例，疗效是确切的。本实验在复习文献的基础上，设计了犬下颌骨颊向牵张成骨机理的研究课题，旨在探讨下颌骨颊舌向牵张的可行性，为三维牵张提供一定的实验基础。
本实验将12只犬下颌骨左侧单皮质骨方块截骨，安置半埋置型牵张器，延迟7天后，以2次/天，0.5mm/次的速度向颊侧牵引，延长7天后固定，右侧截骨后不牵引做为对照。分别在固定后第4天、第1、2、4、6、8周等时段取材，多聚甲醛固定。脱钙后行常规HE及改良Mallory's三色法染色，结果示左侧牵张区明显向颊侧隆起7mm，牵张区有大量新骨形成，至8周时钙化良好，x线显示与周围正常骨相连续。而对照组则
第四军医大学硕士学位论文
为正常骨折愈合过程。
另取材不脱钙，行成骨组织扫描电镜观察和二线能谱分析钙磷元素
含量变化。结果发现随牵张后固定时间的延长，各实验组钙、磷元素含
量逐渐增高，新骨组织是向着正常骨组织质和量的方向进行矿化，钙磷元
素参与了骨质矿化的全过程。
牵张成骨中有很多生长因于参与，本实验观察了各个时段整合素el
在新骨成骨细胞和破骨细胞上的表达，发现其在不同时段的表达水平不
同。成骨细胞膜上整合素pl在牵张后第一周开始表达，第2－4周表达最
强，第8周恢复正常水平。破骨细胞在第4天弱阳性表达，一周后明显抑
制，第4周基本消失。初步论证其可能介导了牵张中机械应力信号转导。
有关其与其它信号分子间的相互作用以及对其介导的细胞内应力信号
（第二信号通道）传递有待作进一步的研究。
总之，本课题的实验结果表明下颌骨颊舌向牵张成骨是可行的，其
组织学变化与前后向、垂直向牵张相似。扫描电镜及能谱分析提示颊舌
向牵张过程符合DO基本原则，固定至4－6周可考虑拆除牵张器，至8周时
可行使正常生理功能。CI、P元素参与了牵张的整个过程。整合素el可
能介导了机械应力转导，将机械信号转化为成骨信号。以上结果为临床
颊向牵张治疗偏面小颌畸形提供了有效的实验依据。
The congenital or acquired deformity and defect, esp the deformity of mandible, is common in clinic. Most of them were caused by postoperation, trauma and inflammation, leading to dysfunction and physiognomy malformation. From 1992, McCarthy firstly introduced the use of extraoral distractor to treat deformity of mandible, distraction osteogenesis became an important method to correct oral and maxillofacial underdevelopment and formities of facial skeleton.
Many animal experiments and clinic cases have been reported to investigate the medial-distal and vertical distraction in recent years. Such as dysostosis, defect of mandible,micrognathia,OSAS,palate cleft and so on.At the bottom of many reviews, this study designed bucco-lingular distraction of canine's mandible,in order to inquiry the possibility of bucco-lingular distraction.Also,the study might supply a experimental basis of three-dimensional distraction.
In this experiment, a half-buried distractor has been used after the square osteotomy to unilateral cortical bone of twelve canine's bilateral mandible. The bone segment of left mandible was elongated buccally after a consolidation phase of 7 days. The distraction protocol consisted of a rate of 0.5mm twice daily for 7 days, while right bone segment didn't proceed
distraction as control. The new osteogenesis were obtained and decalcified and paraffin slices were made respectively on the 4th day, the 1st, 2nd, 4th, 6th, 8th week after distraction complete. The slices were stained with HE and modified Mallory's. The results indicated that the left distraction segment obviously eminence buccally. The newly generated bone could be observed in distraction gap and it calcificate well at 8th week. The newly bone were continuous with circumference normal bone.
Other specimens didn't decalcify and processed for SEM evaluation and Ca/P ratio assay.With elongation time of the consolidation,the contents of Ca, P bundle were found to be elevated in the experiment. The newly generated bone decalcified as well as nomal bone with the maturity of distracted callus. It also shows that Ca, P element took part in the whole procedure of bone generation.
Many growth factors have been proved to produce a marked effect on
DO. In this study, The expression of integrin β1 in bone tissue, especially in the membrane of osteoblast and osteoclast was detected differently. In
osteoblasts, integrin β1 expressed increased on the 1 st week, maximum on the 2nd~4th week and normal on the 8th week. In osteoclast, inferior positive expression of integrin β1 was observed on the 4th day, decreased on the 1 st week and disappeared on the 4th week.The increased expression of integrin β 1 in osteoblast suggested that integrin β1 has a critical influence on distraction osteogenesis, and likely relates to the mechanical signal transduction. The interaction of the integrin and other signal molecul and the strain delivering from inter-cells should be studied further and deeply in future.
In general, the experiments in this study showed that bucco-lingular
distraction is feasible and coincident with the principle of DO by XRS. The Ca, P element had been proved to participate the whole distraction. Integrin β1 probably took part in transducting the mechanical signal to osteogenesis's signal.The results of the study might provide effective basis on treating HFM in clinic.
引文
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