正颌外科手术后的系统性骨加速现象及其机制研究

In recent years, “Surgery First Approach (SFA)” in surgical-orthodontic treatment accelerated orthodontic tooth movement, has been proposed as a novel approach. However, the underlying mechanisms of SFA accelerating tooth movement have not been well understood. In our previous researches, we have observed that the Systematic Acceleratory Phenomenon (SAP) in rabbits has accepted following mandibular ramus osteotomy as: 1)the bone density of alveolar bone beyond the surgical site had reduced; 2) a couple of osteoclast cells had been found on alveolar bone. In addition, we have also observed the accelerated bone metabolism in the patients undergoing orthognathic surgery. Furthermore, we have tried to explain how orthognathic operations influence the bone remodeling: 1) we follow up the patients after operation with blood test and Micro-CT; 2) set up a postoperative rabbit model to test the function of IL-1,IL-6,TNF-α in SAP in-vivo and in-vitro. Based on above findings, we expect to elaborate the theory behind SAP and accelerated tooth movement induced by orthognathic surgery.

近年来,正畸正颌联合治疗中“手术先行”的治疗方式(Surgery First Approach,SFA)因可以加快术后正畸牙移动,而作为一种新的治疗模式被提出。但SFA加速牙移动的机制仍未阐明。我们推测系统性骨加速现象是其可能的机制 ,并在前期研究中得到证实:下颌骨体部截骨后,在远离截骨区域的前牙牙槽骨发生骨密度下降,破骨细胞产生;进一步研究发现正颌手术导致患者体内骨代谢水平的升高。为了阐明正颌术后SAP导致牙移动加速的机理,我们应用MicroCT,组织学,细胞及分子生物学等手段,从临床研究、动物实验、细胞水平三个方面,揭示正颌手术对机体骨代谢的影响,正颌术后SAP发生的时空规律,正颌术后产生的TNF-α,IL-6,RANKL等在激发SAP发生中的作用机制。阐明这些机制,为术后正畸中充分利用SAP加速牙移动,缩短疗程提供理论支持。

本课题从临床研究、动物实验、细胞实验三个方面，通过对正颌术后患者血清中骨代谢标志物、白细胞介素6（Interleukin-6，IL-6）等变化和系统性骨加速（Systemic acceleratory phenomenon，SAP）影像学表现的研究；建立大鼠上颌正畸牙移动模型、小鼠下颌骨截骨术模型及家兔下颌骨截骨术模型，对正颌术后系统性和局部性骨加速现象，以及对牙移动的影响进行研究；通过细胞共培养等技术对IL-6等炎症因子和缺氧诱导因子1α（Hypoxia induction factor 1 α，HIF-1α）影响骨细胞及破骨细胞进而调节骨加速现象进行研究。得出以下结论：正颌术后患者血清中炎症因子IL-6 与核因子-κB受体活化因子配体（receptor activator of nuclear factor-κ B ligand, RANKL）在术后3-7天表达显著升高；手术先行术后牙移动加速现象的内在机制可能为正颌手术透过上调血清中骨改建相关因子表达水平，加速系统性骨代谢，激发调控破骨过程重要信号分子单核细胞集落刺激因子（Monocyte colony stimulation factor，M-CSF）及RANKL，进而影响牙移动速率；IL-6等炎症因子及HIF-1α在正颌术后局部骨加速现象中有重要作用；IL-6可通过JAK2-STAT3 信号通路实现RANKL的表达增加从而促进骨细胞介导破骨细胞生成。本研究揭示了正颌手术系统性骨加速现象和局部骨加速现象对机体骨代谢的影响，以及正颌术后骨加速现象发生的时空规律；术后IL-6、RANKL等炎症因子和HIF-1α水平变化后改变骨细胞和破骨细胞生物学行为的细胞机制和分子机制。阐明这些机制,为术后正畸中充分利用系统性骨加速现象和局部骨加速现象加速正畸牙移动，缩短疗程提供理论支持。