外周神经在低幅高频振动对抗废用性骨质疏松中的作用

Disuse osteoporosis is defined as localized or generalized bone loss resulting from reduction of mechanical stress on bones. Anything that reduces the mechanical stress on bones can cause disuse osteoporosis, such as illness necessitating bed rest, spinal cord injury, paralysis from stroke. Even astronauts who experience prolonged weightlessness can develop disuse osteoporosis.It's well known that the mechanical signal enhances osteogenesis, and the low-magnitude high-frequency vibration has been used to prevent disuse osteoporosis. However, the mechanism underlying the modulatory effect of low-magnitude high-frequency vibration on bone metabolism remains unclear. Our previous study indicated that peripheral innervation in bone may play am important role in bone metobolism, implying that peripheral innervation may participate in the preventing effect of low-magnitude high-frequency viberation on disuse osteoporosis. In the present study, by using the tail-suspending rat as the disuse osteoporosis model. the influence of low-magnitude high-frequency vibration on the sensory neuron secretion in dorsal root ganglion and the sensory nerve fiber distribution in tibia will be studied. Then the influence of sensory nerve innervation on preventing effect of low-magnitude high-frequency vibration on disuse oestoporosis will be further confirmed by comparing the preventing effects of low-magnitude high-frequency vibration on disuse osteoporosis with and without sensory nerve block.The proposed study can deepen our understanding of the mediating effect of peripheral innervation in mechanical stimulation-modulating bone metabolism, which may broden the physithery methods for bone-related disease, providing patients with more safe and effective physical interventions in rehabilitaton.

废用性骨质疏松是由于机械应力对骨的作用降低而导致的局部或者全身的骨量减少、骨质量降低，是危害人类生命健康最严重的疾病之一。研究证实，低幅高频振动具有显著的成骨效应，可用于对抗废用性骨质疏松，但其中的机理仍不得而知。我们的前期研究证实，神经对骨代谢具有重要的调节作用,提示外周神经可能介导了低幅高频振动对抗废用性骨质疏松的作用。本课题拟利用尾悬吊大鼠废用性骨质疏松模型，通过ELISA定量和免疫荧光染色方法,分析机械振动对背根神经节CGRP阳性感觉神经元分泌及胫骨骨骺和骨干CGRP阳性感觉神经纤维分布的影响，探讨感觉神经与骨质疏松的关系。并通过感觉神经失活对低幅高频振动对抗骨质疏松作用的影响，进一步论证外周感觉神经在介导机械刺激调节骨代谢中的作用，揭示低幅高频振动促进骨生成的作用机制。本研究将有助于拓宽骨相关疾病干预治疗的康复理疗手段，为患者的康复提供新型、有效、可靠的干预策略。

低幅高频振动所产生的机械应力刺激可以有效的促进骨生成，并可作为对抗废用性骨质疏松的有效干预手段，但其中的机理仍不得而知。近年来，骨组织中分布的CGRP感觉神经纤维对骨代谢的调控，越来越受到关注。离体实验也证实，CGRP可以和成骨细胞及破骨细胞受体结合而调节骨代谢。本课题通过感觉神经失活，研究了CGRP感觉神经支配与废用性骨质疏松的相关性，同时探讨了低幅高频振动对抗废用性骨质疏松的神经反馈调控机制。本课题利用外周骨定量CT、显微CT、组织形态计量学、骨组织HE染色、成骨细胞ALP及破骨细胞Trap染色等手段首先明确了尾悬吊废用性骨质疏松模型的有效性，通过免疫荧光、ELISA等分析和辣椒素神经阻滞发现尾悬吊大鼠胫骨废用性骨质疏松进程与CGRP阳性神经的去支配作用化具有很强的相关性。低幅高频振动（频率35Hz,振幅0.3g)治疗4周及8周，显著抑制了骨质疏松程度，同时骨组织内CGRP感觉神经纤维密度较悬吊无治疗大鼠明显升高。利用辣椒素进行CGRP感觉神经阻滞后，低幅高频振动对抗骨质疏松的效果明显减弱。以上结果表明低幅高频振动通过促进外周感觉神经纤维CGRP分泌调节骨代谢，从而有效对抗废用性骨质疏松。本课题进一步明确了感觉神经支配对于骨代谢的重要作用，CGRP也成为治疗骨相关疾病重要的药物靶点，同时也为优化康复理疗手段，为患者提供新型、有效、可靠的干预策略提供了借鉴。