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

交感神经系统治疗骨损伤新疗法的实验研究

基本信息

批准号：
20300158
负责人：
MATSUMOTO Takeshi
金额：
$ 9.4万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

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.

骨折治疗后早期下床活动可有效减轻废用介导的骨萎缩，从而防止老年人卧床不起或骨质疏松症，并协助青少年的健康骨骼发育，以降低未来骨质疏松症的风险。通过β-肾上腺素能系统进行骨折治疗，特别是在愈合的早期阶段。在麻醉的大鼠中，在胫骨骨干中产生全层单皮质缺损，并且通过尾部悬吊实现后肢卸荷。将动物分为三类：用普萘洛尔进行β-肾上腺素能阻断（PRO）治疗，并在五天或十天后用去铁胺治疗以增强血管生成。手术中，从腹主动脉注射氧化锆-琼脂糖造影剂，然后切出缺损区域，并用 17. 1 同步加速器光扫描。 18. 减影 CT 为 1 keV，分别位于氧化锆 k 边缘的正下方和上方。术后五天，新形成的血管的体积分数明显较高，但仅趋于趋向。 PRO 中的值高于 C 中的值。手术后 10 天，两种治疗对骨再生均无影响，三组中的血管生成进展到相似程度，但再生骨的体积分数明显更高。 DFO 但仅在 PRO 中比在 C 中更高。需要进一步研究 β-肾上腺素能阻滞剂的有效浓度或选择性，以使其有益利用。