【作者】 柳玉晓；

【导师】 刘彦普； 赵晋龙；

【作者基本信息】 第四军医大学 ， 口腔临床医学， 2009， 博士

【摘要】 肿瘤及类肿瘤病变是近年来颌面部获得性畸形或缺损的主要原因之一,常常造成不对称性畸形与不规则的组织缺损,导致外貌缺陷与功能障碍。影响患者正常的学习、工作和社交。因此,合理选择整复技术,最大限度恢复其容貌和生理功能,是口腔颌面外科面临的重要任务之一。口腔颌面部肿瘤手术造成的软硬组织缺损修复是临床上一个比较棘手的问题。髂骨移植和带蒂腓骨瓣转移被证明是有效的外科手段,但是它们会不可避免的造成其他相关区域的骨缺损和机能缺失。牵张成骨技术作为一种新的方法已经成为颌面整形修复的重要手段,并逐渐被应用于颌骨缺损的整复。但颌骨恶性肿瘤手术后,经常需要放疗,往往造成颌骨缺损合并放射损伤。关于放疗后牵张成骨修复颌骨缺损,文献报道较少,但其意义显而易见。它也是困扰大多数临床医师的一个难题。本研究的目的在于建立实验室可控条件下的放疗后牵张成骨动物模型,并在此基础上对放疗后可行牵张成骨的剂量范围及下齿槽神经的电生理变化进行探讨,以期为临床应用提供理论依据。研究包括三部分:第一部分:下颌骨放疗后牵张成骨狗实验动物模型的建立及评价目的是建立牵张成骨狗实验动物模型,为进一步研究提供依据。本实验共使用了8只健康成年中国杂种犬。6只动物单侧下颌接受总量为22.8Gy,5.7Gy/4次/2周(相当于50Gy/25次/5周)的60Co照射后,经3个月,对照射侧下颌骨及对照组2只狗单侧下颌骨分别植入牵张器,经5天延迟期,以0.5mm/次,2次/天的速度牵张下颌骨10天,然后固定8周。观察动物耐受情况。结果除一只因麻醉意外死亡外,其余动物下颌骨均被成功延长,动物能够耐受放射照射、手术,组织学及SPECT检查均表明牵张区新骨生成。中国杂种犬是一种理想的放疗后牵张成骨模型动物。第二部分:不同放射剂量下牵张成骨的可行性研究正常颌骨肿瘤手术后放疗总剂量约为50～70Gy。因为50Gy通常被认为是产生骨损伤的临界剂量,所以本实验采用50Gy,60Gy,70Gy三种剂量(转化为相应生物学等效剂量)观察放疗后牵张下颌骨成骨情况。14只中国杂种犬随机分为A、B、C、D四组,A,B,C组为实验组,每组4只,单侧下颌A组接受总剂量22.8Gy,5.7Gy/4次/2周(相当于50Gy/25次/5周),B组接受总剂量24.8Gy,6.2Gy/4次/2周(相当于60Gy/30次/6周),C组接受总剂量27.2Gy,6.8Gy/4次/2周(相当于70Gy/35次/7周)的60Co放射照射。照射完成后3个月,各组分别于照射区行下颌骨切开术,置入牵张器,D组2只动物,为对照组,亦植入牵张器。经五天延迟期,以0.5mm/次,2次/天的速度牵张下颌骨10天,然后固定8周。实验组于牵张完成即时,固定8周后每组分别处死2只动物,对照组分别于牵张完成即时、固定8周后各处死1只动物,行大体观察,放射学,组织学检查。结果动物下颌骨均被成功延长,但成骨情况不同,A,B,D组成骨良好,C组成骨情况差。神经组织亦显示相应变化。结果显示在一定的治疗程式下,50Gy和60Gy是牵张下颌骨成骨的安全剂量,70Gy放射剂量下牵张成骨须谨慎。第三部分:放疗后牵张成骨下齿槽神经电生理变化的实验研究探讨放疗后下齿槽神经的电生理变化。12只中国杂种犬随机分为A、B、C三组,A,B,C组为实验组,每组4只,单侧下颌A组接受总剂量22.8Gy,5.7Gy/4次/2周(相当于50Gy/25次/5周),B组接受总剂量24.8Gy,6.2Gy/4次/2周(相当于60Gy/30次/6周),C组接受总剂量27.2Gy,6.8Gy/4次/2周(相当于70Gy/35次/7周)的60Co放射治疗。放疗完成后3个月时,各组分别于放疗区下颌骨切开,置入牵张器。经五天延迟期,以0.5mm/次,2次/天的速度牵张下颌骨10天,然后固定8周。分别于放疗前、放疗结束后、牵张前、牵张第六天、牵张完成即时、固定第2,4,8周8个时间点以神经电生理检诊仪测定神经电生理变化。结果50Gy和60Gy组动作电位呈现适应性变化,70Gy组不能完整导出动作电位。提示低剂量放疗不会单独对神经电生理变化造成影响,高剂量放疗会严重损害神经。更多还原

【Abstract】 Tumor and tumor-like diseases is one of the main reasons of acquired deformity and defects in maxillofacial surgery.They often cause anisomerous deformity and irregular defects of the tissue,which often result in disfigurement and dysfunction.It is important for maxillofacial surgeons to find ways to resolve the problem.Repairing the irradiated facial bone defects,especially caused by tumors,has been a problem for oral and maxillofacial surgeons for a long time. Iliac and fibula transplantation have been proved successful approachs by surgeons. But these techniques also resulted in inreversible defects of other bones.Nowadays, distraction osteogenesis(DO) has become a regular way in reconstruction of craniofacial deformity,but seldom recorded in use in irradiated bone defects. Recently, experiments showed DO should also be a potential way to repair the irradiated mandible. However,there are still many problems about DO in irradiated mandible,such as the character of the new bone,the adaptability of the inferior alveolar nerve (IAN), et al.In this study, we intended to establish an animal model of distraction osteogenesis in the irradiated dog mandible for further study in this field. And with this kind of model, the scope of the irradiation doses that can achieve successful DO and the electrophysiological changes of the irradiated IAN were also studied.Three parts were included in this study.Part 1 Establishment of an animal model of distraction osteogenesis in the irradiated dog mandible and the study of its characteristicsTo explore the character of distracted bone in the irradiated dog mandible and the corresponding change of the irradiated inferior alveolar nerve(IAN) in order to establish an animal model. Eight Chinese dogs were used in this study. Six dogs received a unilateral irradiation from 60Co(group R) in the mandible with a total dose of 22.8Gy in four 5.7Gy fractions (biologically equivalent to 50Gy/25 fractions).The other two dogs without irradiation served as control (group C). Bilateral corticotomy was made 3 months after completion of irradiation. After a 1-week latency period,bone distraction was activated at a rate of 0.5mm twice daily for 10 days, followed by a consolidation phase of 8 weeks. New bone underwent radiographic,histological and single photon emission computed tomography (SPECT) analysis. One dog was excluded from the study due to anaesthetic in group R. After 8 weeks of consolidation, no difference was found between the percent area of new bone in both groups. New bone was more mature and organised in group C than in group R.SPECT analysis showed there are active osteogenic activity in group R. We established the animal model of distraction osteogenesis in the irradiated dog mandible.Part 2 Feasibility of distraction osteogenesis in the dog mandible under different radiographic dosesTo test the safety doses of distraction osteogenesis(DO) in the irradiated dog mandible.14 Chinese dogs were used in this study. They were randomly divided into 4 groups.Group A,B,C own 4 dogs respectively served as experimental groups while group D own 2 dogs served as control group.Group A received a unilateral irradiation from 60Co in the mandible with a total dose of 22.8Gy in four 5.7Gy fractions (equivalent to 50Gy/25 fractions).Group B receieved a unilateral irradiation from 60Co in the mandible with a total dose of 24.8Gy in four 6.2Gy fractions (equivalent to 60Gy/30 fractions). Group C receieved a unilateral irradiation from 60Co in the mandible with a total dose of 27.2Gy in four 6.8Gy fractions (equivalent to 70Gy/35 fractions). Bilateral coticotomy was made 3 months after completion of irradiation. After a 1-week latency period, bone distraction was activated at a rate of 0.5mm twice daily for 10 days, 2 dogs sacrificed just after distraction and the other 2 dogs sacrificed after 8 weeks of consolidation in group A,B,C while 1 dog sacrificed just after distraction and another dog sacrificed after the same consolidation period in group D. New bone underwent radiographic, histological histomorphometric analysis. All dogs were successfully distracted in this study.After distraction,osteogenic activity was detected in group A and group B.After 8 weeks of consolidation, no difference was found between the percent area of new bone in group A and group B.New bone formation was not evident in group C. New bone was more mature and organised in group D than in group A and B. Larger chondroid islands were found evident in distracted bone of group D. It seems that DO can be feasible in previously irradiated dog mandible, 50Gy and 60Gy are the safety doses, 70Gy should be cautiously selected.Part 3 Experimental study of distraction osteogenesis in the irradiated dog mandible :the electrophysiological changes of IANWe proved the feasibility of DO under different radiographic doses through histological analysis and gross specimens in former experiment,but it is not enough for IAN. Another important criteria of IAN is its electrophysiological alternation. We explored the electrophysiological changes of IAN during DO. 12 Chinese dogs were randomly divided into 3 groups--group A,B,C.Each group own 4 dogs respectively.Group A received a unilateral irradiation from 60Co in the mandible with a total dose of 22.8Gy in four 5.7Gy fractions (equivalent to 50Gy/25 fractions) within two weeks.Group B receieved a unilateral irradiation from 60Co in the mandible with a total dose of 24.8Gy in four 6.2Gy fractions (equivalent to 60Gy/30 fractions) within two weeks. Group C receieved a unilateral irradiation from 60Co in the mandible with a total dose of 27.2Gy in four 6.8Gy fractions (equivalent to 70Gy/35 fractions) within two weeks. Bilateral coticotomy was made 3 months after completion of irradiation. After a 1-week latency period bone distraction was activated at a rate of 0.5 mm twice daily for 10 days, followed by a consolidation phase of 8 weeks. During the experiment, 8 time-points was chosed to examine, record and analyze the evoked potentials(EP) of IAN:pre-irradiation,post-irradiation,pre-distraction,the sixth day amid distraction, post-distraction, the 2th, 4th, 8th week during consolidation.The neural electricity tester (Type NDI-200P+,Shanghai Haishen electronic medical Co,Ltd ) was adopted to each group to carry out the electrophysiologic analysis. At each time-point,one needling electrode was stabed in foramen mentale as activate electrode,while another needling electrode stabed in the mandibular skin 1cm away from the activate electrode as reference electrode.Near the foramenmandibulae,we stabed in receive electrode and 2cm away from it another needling electrode was used as indifferent electrode.The grounding electrode was placed in the anterior leg.39.8mA as activate current,the evoked potential was recorded. The action potential(AP) of IAN showed corresponding change during the irradiation and distraction process in group A and B,but group C did not got integrated AP. They are coincident to the change of the bone.更多还原