【作者】 刘伟；

【导师】 归来；

【作者基本信息】 北京协和医学院 ， 外科学， 2012， 博士

【摘要】 目的：下颌骨外板截骨术是近年来临床上兴起的一项技术。该术式对于儿童患者是否可行?是否会影响下颌骨正常的生长发育?尚缺少相应的实验数据。我们在前期实验中,以3月龄小型猪为研究对象,截除单侧下颌骨体部外板,部分动物(37.5%)术后出现下颌偏颌畸形。在本实验研究中,我们重点探讨骨膜在骨创面愈合与骨重建过程中的重要性以及骨膜因素与实验动物术后出现下颌偏颌现象的关系。方法：实验分两部分。第一部分,3月龄小型猪分四组。A组,左侧下颌骨体部外板截除术,同时切除下颌体部骨膜；右侧下颌骨体部外板截除术,保留骨膜。B组,左侧下颌骨体部外板截除十骨膜切除。C组,对照组,仅行右侧下颌体部骨膜下剥离。D组,空白对照组。于术前、术后行头颅CT扫描、三维重建与测量,观测、总结幼龄猪下颌骨外板截除术后下颌骨形态学变化及偏颌畸形发生的规律。第二部分,实验动物分两组：A组与B组(同第一部分)。术后4周、12周、24周行下颌骨体部HE染色、免疫组化染色及扫描电镜检测。从组织学与超微结构角度,论证实验动物下颌骨外板截骨术后下颌偏颌现象与骨膜因素的关系。同时,从成骨与破骨(BMP-4,OPG/RANKL),骨细胞凋亡(Ki-67, caspase-3)和骨免疫学(CD3,CD19)等角度,进一步探讨实验动物下颌偏颌现象与骨膜因素的关系。结果：第一部分,A组,66.7%实验动物出现较明显的下颌偏颌畸形,均偏向保留骨膜侧。发生时段：术后3-6个月。C组,100%出现轻微的偏颌畸形,均偏向健侧。发生时段：术后3月内。B组、D组未出现偏颌畸形。幼龄猪下颌骨体部外板截骨术对下颌骨生长发育的影响主要在于下颌体部,表现为局部长度的异常。第二部分,正常情况下,骨外侧皮质的骨重建是幼龄猪下颌骨的主要生长方式之一。下颌骨体部外板截除术后,保留骨膜侧骨创面的愈合明显优于切除骨膜侧。保留骨膜侧成骨方式为膜内成骨,而切除骨膜侧成骨方式为软骨内成骨。下颌骨体部外板截除术后,骨创面愈合及骨重建过程中,BMP-4, OPG, RANKL, caspase-3等细胞因子的表达明显异于正常,其成骨/破骨的动态平衡受到破坏,导致下颌骨的异常生长。切除骨膜侧尤为明显。结论：①骨膜在骨创面愈合与骨重建过程中发挥重要作用。②幼龄猪下颌骨体部外板截骨术会抑制下颌骨的生长发育,骨膜因素是其主要原因之一。更多还原

【Abstract】 Background:Mandibular outer cortex osteotomy is an emerging clinical technique. Is it feasible to perform mandibular outer cortex osteotomy in children? Will the removal of the mandibular outer cortex in children affect the normal growth of the mandible? Very few animal studies and clinical experiments have addressed these issues. In the previous study, we used young miniature pigs as experimental animals. Unfortunately, some animals (37.5%) exhibited mandible deviation after outer cortex osteotomy of mandibular body. The aim of this study was to evaluate the role of periosteum on the healing and growth of mandible after the operation and the relation of periosteum and mandible deviation.Methods:This experimental study included two parts. In the first part, three-month-old miniature pigs were used as experimental animals and were randomised into four groups. Experiment A:The osteotomy was performed on both sides. At the same time, the periosteum around mandibular body was excised on the left side. Experiment B:The osteotomy was performed on the left side with periosteum excised. Experiment C: Subperiosteal stripping was performed on the right side. Experiment D:Blank control. The morphology of skull and mandible was analysed using3D-CT technique before and after surgery to evaluate the relation of periosteum and mandible deviation. In the second part, the experimental animals were randomised into two groups. Experiment A:The osteotomy was performed on both sides. At the same time, the periosteum around mandibular body was excised on the left side. Experiment B:The osteotomy was performed on the left side with periosteum excised. The histologic analysis of HE stain, immunohistochemical staining and electronic microscope scanning was evaluated at4,12and24weeks after surgery. From the view of bone formation/bone resorption, apoptosis and osteoimmunology, the role of periosteum on the healing and growth of mandible and the relation of periosteum and mandible deviation were evaluated.Results:In the first part, some animals (66.7%) exhibited obvious mandible deviation after surgery in experiment A, which occurred on3-6months after surgery. In experiment B and D, no mandible deviation was observed. All the animals exhibited slinghtly mandible deviation after surgery in experiment A, which occurred at3months after surgery. The influence of periosteum on the development of mandible after surgery occurred in the body of mandible. In the second part, we found the bone wound healed well on the side with periosteum while poor without periosteum. The osteogenesis mode was intramembranous ossification on the side with periosteum and endochondral ossification without periosteum. During the bone wound healing and bone remodeling, the expression of bone morphogenetic protein-4, osteoprotegerin, receptor activator for nuclear factor kappa B ligand, caspase-3and so on was different from normal. The balance between bone formation and bone resorption was unable to maintain after surgery and the imbalance interfered with normal bone growth, especially on the side without periosteum.Conclusion:Firstly, periosteum played an important role on the bone wound healing and bone remodeling. Secondly, mandibular outer cortex osteotomy would inhibit the development of mandible. The periosteum was one of the major factors causing post-operative mandible deviation.更多还原