基于错颌畸形矫治与慢性氟中毒损伤的生物学机制矛盾研究丹参干预染氟大鼠正畸牙移动的作用

During the treatment of malocclusion, the key of moving teeth is ​​degradation and remodeling of periodontal ligament’s collagens, capillaries angiogenesis, stronger function for osteoclasts than for osteoblasts of alveolar bone,and more bone resorption than formation in pressure zones, induced by periodic force. While all the time under the chronic fluorosis, there is a pathological basis including that collagen synthesis of fibroblasts was enhanced, the differentiation to osteoblasts was obvious, the function of vascular endothelial cells was impaired, the osteogenic activity was stronger than that of osteoclasts and bone formation was more than resorption. Thus, there exists contradiction on tendency of the two biological mechanisms of bone turnover..In our research group，we have found through clinical observation that it was relatively a bit difficult for malocclusion patients with chronic fluorosis while moving their teeth. It’s helpful for recovering or even promoting tooth movement together with Danshen，but lack of definite basic research evidence at present..Relying on the following studies: the spatial relationship between jaw and teeth, cytological mechanisms of the orthodontics, anti-oxidative effects of Danshen and the previous study on promoting orthodontic tooth movement assisted by Danshen, the objective of our study is to verify the intervening action of Danshen on orthodontic tooth movement with chronic fluorosis, to explore the possible mechanism, and to supply clinical applying evidence for orthodontic treatment plan combining using traditional Chinese and Western medicine..Our study method is going to take use of Micro CT, real-time quantitative PCR, et al, and through the following aspects：tooth movement speed, antioxygenation，morphology，collagens and blood vessels, bone formation and resorption, and regulation of gene expression of the bone turnover axis(RANKmRNA, RANKLmRNA and OPGmRNA).

错颌畸形正畸治疗时，牙齿得以移动的关键是矫治力周期性地引导压力区牙周膜胶原纤维有序降解并重塑、微血管新生、牙槽骨破骨细胞功能强于成骨细胞、骨吸收大于骨形成；而慢性氟中毒时，机体持续存在成纤维细胞胶原合成增强、成骨方向分化明显、血管内皮细胞功能受损、成骨细胞功能强于破骨细胞、骨形成大于骨吸收的病理基础。因此两者骨转换倾向的生物学机制存在矛盾。课题组发现慢性氟中毒患者正畸治疗时牙移动困难，而合用丹参有恢复牙移动速度的作用，但缺乏基础研究依据。因此，依托牙颌空间关系、正畸力学机制、丹参抗自由基和加速正畸牙移动的前期研究基础，本课题拟采用显微CT、荧光实时定量PCR等手段，从牙移动、抗氧化、组织形态、胶原与血管、骨形成与骨吸收、骨转换轴基因（RANK、RANKL和OPGmRNA）表达调控等方面，研究丹参对慢性氟中毒大鼠正畸牙移动的干预作用，并探索其机制，为该病的中西医结合正畸治疗方案提供应用证据。

正畸治疗是口腔临床治疗中重要的组成板块，高度依赖颌骨及牙周骨组织生物状态。慢性氟中毒是骨相损害为主要表现的全身累及性毒性病变，但现有研究一直忽略对口颌面部骨相氟毒损害的系统观察，对于像贵州这样的高氟病区生活人群接受口腔治疗无疑是缺乏针对性策略和措施的。而传统中医药具有自身特殊的普遍适应性和治疗普惠性。因此，本研究既关注了颌面部公共卫生健康问题又巧妙结合中西医诊疗优势，具有较敏感的探索思路。. 本项目从三个层次探究了慢性氟中毒环境对大鼠颌骨及牙周组织的影响及中药丹参的干预作用：①慢性氟中毒环境下,大鼠颌骨及牙周组织氟蓄积增高，且高于四肢长骨股骨氟离子含量。相较于股骨，颌骨更表现持续蓄氟的能力。提示受到的氟毒损害可能更显著、更持久。成骨和破骨功能失调，骨微结构紊乱，骨小梁异常崩解，小梁间联结混乱；颌骨微循环障碍，抗氧化损伤能力下降 ②慢性氟毒环境下正畸牙移动改变。相较于生理环境下正畸牙移动，氟毒大鼠牙移动速率减慢，牙移动总位移保持。周期速率改变，主要表现在第二快速移动期的加速移动，提示可能影响牙移动后的稳定性恢复。组织学显示破骨细胞生成受抑制，牙移动速率减慢。颌骨骨微结构显示，氟毒大鼠骨小梁数目增多，小梁崩解，联结性减弱，骨微结构质量减弱。③丹参干预慢性氟中毒环境正畸牙移动大鼠牙周组织骨改建。丹参作用下，氟毒大鼠牙移动速度有所恢复，但仍慢于生理环境大鼠牙移动表现。丹参通过影响骨转换轴RANK/RANKL/OPG表达及调节比值关系，恢复破骨细胞功能，从而促进牙移动速率的恢复。因此，丹参具有确定的干预正畸大鼠受氟毒损害的作用。由于丹参的干预作用呈一定浓度和时间依赖关系，具体的剂量指导还需进一步的研究探索。. 本研究描述了过量氟离子对颌骨及牙周骨组织损害的病理过程，验证了中药丹参对氟毒损伤的干预及牙周组织改建恢复作用，对于利用中西医结合策略解决慢性氟中毒患者正畸治疗的特殊需求将具有十分重大的医学意义和科学价值。