低强度脉冲超声波在TMD治疗中的作用及相关机制研究

Temporomandibular joint disorder（TMD） is a frequently occurring disease and there is no ideal treatment now. Studies have proven that hypoxia exists in the articular cavity of patients with temporomandibular joint disorder for a long time. Hypoxia adjusts the expression of MMPs and other genes in articular disc, which is one of the causes of temporomandibular joint disorder. The preliminary studies of our research group found that hypoxia promoted the vascularization of articular cartilage and the expression of several inflammatory factors and angiogenic factors of articular chondrocyte under. hypoxia up-regulated, which further worsened TMD. After the intervention with low intensity ultrasound, it is found that the proliferation and differentiation of mandibular condylar chondrocyte enhanced and the expression HIF-1 and VEGF down-regulated, indicating that low intensity ultrasound significantly improved the hypoxia of mandibular condylar chondrocyte. What is the specific mechanism? The biological effect and action mode of ultrasound on chondrocytes remain unclear. Based on the preliminary studies and combined with Micro-CT, molecular biology and other technologies, this study is to screen out the optimal action mode of ultrasonic signals as well as define the function and mechanism of ultrasound on hypoxia of mandibular condylar chondrocyte. This study is expected to illuminate the new mechanism of ultrasound on improving hypoxia of mandibular condylar chondrocyte and open new application field for ultrasonic therapeutics, which is of important theoretical significance and potential application value.

颞下颌关节病（TMD）是口腔颌面部的一类常见病和多发病，其主要临床表现为髁突软骨炎症、退行性变和软骨血管化。目前针对TMD的治疗方法主要以针对咬合因素或心理因素的诱因治疗为主，缺少对损伤部位的直接治疗手段。低强度超声（LIPUS）作为一种非侵袭性临床治疗手段，在骨折愈合、神经损伤修复和促进子宫平滑肌收缩等方面具有明显的治疗作用。本课题组前期研究发现，LIPUS可以减轻大鼠TMD炎症症状，下调HIF-1表达，同时降低髁突软骨血管化程度，但具体作用机制如何尚不清楚。针对上述问题，本课题拟在前期建立的大鼠TMD模型基础上，综合形态学、分子生物学等方法筛选出LIPUS治疗TMD的最佳方案，明确LIPUS减轻TMD髁突软骨血管化及改善细胞低氧状态的治疗作用，探讨LIPUS治疗TMD的分子机制，为深入研究TMD的发病机制和防治措施提供新的理论依据，也为LIPUS技术在医学领域的应用提供新的实验依据。

颞下颌关节紊乱症（TMD）是口腔颌面部的一类常见和多发病症，其病程复杂，多表现为功能紊乱，严重者可出现关节结构破坏。目前，TMD的无创治疗方法以针对咬合或精神因素的诱因治疗为主，尚缺乏对损伤部位的直接治疗手段，常使局部症状不能快速有效的缓解。低强度脉冲超声治疗（LIPUS）是近年来新兴的无创物理治疗方法，其采用强度小于100mW /cm2的脉冲式超声波直接作用于患处，通过声流或声微流等机械作用产生多种生物学效应，在加速骨折愈合、神经损伤修复、促进软组织微循环等方面具有明显作用。前期研究发现LIPUS可以促进软骨细胞增殖，其对于关节软骨损伤也具有一定治疗效果。但LIPUS众多参数如强度、频率、作用时间等的不同，都会影响其生物学效应，究竟怎样的超声治疗模式对颞下颌关节软骨组织修复最为有利尚无定论，且LIPUS在软骨修复中的作用机理尚不清楚。本研究通过动物及细胞实验研究发现，LIPUS可以有效抑制慢性睡眠剥夺所诱导的大鼠颞下颌关节损伤，45 mW/cm2强度的LIPUS干预2周及以上是大鼠颞下颌关节损伤的最佳治疗方案；LIPUS可以降低大鼠髁突软骨组织中MMP-3/TIMP-1及RANKL/OPG的表达比，抑制MMP-3对髁突软骨基质的裂解活性和RANKL对破骨细胞的激活；低氧微环境中，LIPUS可使髁突软骨细胞HIF-1α上调、HIF-2α下调，进而抑制II型胶原水解，发挥对软骨细胞的保护作用。由此筛选出了LIPUS治疗大鼠颞下颌关节损伤的最佳模式，并在此基础上明确其在髁突软骨修复过程中发挥的作用及分子机制，为未来LIPUS在临床TMD防治中的应用提供了理论依据。