Experimental research on the development of a new therapy for bone injury via sympathetic nerve system

骨折治疗后早期活动可有效减轻废用性骨萎缩，从而防止老年人卧床不起或骨质疏松症，并帮助青少年健康的骨骼发育，降低未来患骨质疏松症的风险。在这项研究中，我们研究了通过β-肾上腺素能系统治疗骨折的潜力，特别是在骨折愈合的早期阶段。在麻醉大鼠的胫骨骨干造成全层单层皮质缺损，并通过尾部悬吊实现后肢卸载。动物被分成三组：不接受任何治疗的大鼠(C)，接受普萘洛尔的β肾上腺素能拮抗剂(PRO)，以及接受去铁胺促进血管生成的大鼠。术后5~10天，动物经腹主动脉注入氧化锆-琼脂糖造影剂。然后切开缺损区，用17.1 keV和181keV的同步加速器扫描，分别位于氧化锆K缘正下方和上方。重建图像被分割成骨和血管。术后5d，DFO组新生血管体积分数明显高于C组，而PRO组仅有高于C组的趋势。两种治疗方法对骨再生均无影响。术后10d，3组新生血管形成程度相似，但DFO组再生骨体积分数明显高于C组，而PRO组仅有高于C组的趋势，β受体阻滞剂的有效浓度或选择性有待进一步研究。

Early postoperative ambulation after fracture treatment is effective in mitigating disuse-mediated bone atrophy, thereby preventing elderly persons from a bedridden state or osteoporosis and assisting healthy bone development of juveniles to reduce the future risk of osteoporosis. In this study, we examined a potential of fracture treatment throughβ-adrenergic system, especially in the early stage of healing. In anesthetized rats, a full thickness unicortical defect was created in a tibial diaphysis, and hindlimb unloading was achieved through tail suspension. The animals were grouped into three categories : rats treated with none(C), with propranolol forβ-adrenergic blockade(PRO), and with desferrioxamine for the enhancement of angiogenesis. Five or ten days later the defect surgery, the animals were injected with zirconia-agarose contrast medium from the abdominal aorta. Then the defect region was cut out and scanned with synchrotron light with 17. 1 and 18. 1 keV for subtraction CT, immediately below and above the zirconia k-edge, respectively. Reconstructed images were segmented into bone and blood vessels. Five days after surgery, volume fraction of newly formed vessels was significantly higher in DFO but only tended to be higher in PRO than that in C. Both treatments had no effect on bone regeneration at this stage. Ten days after surgery, angiogenesis advanced to the similar degree in three groups ; however, volume fraction of regenerated bone was significantly higher in DFO but only tended to be higher in PRO than that in C. Further studies on the effective concentration or selectivity ofβ-adrenergic blockers are needed for their beneficial utilization.