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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，术后早期进行截肢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，并有助于青少年的健康骨骼发育，以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。在麻醉大鼠中，在胫骨骨干中创建全层单皮质缺损，并通过尾部悬吊实现后肢卸载。将动物分为三类：未处理的大鼠（C）、用于β-肾上腺素能阻滞（PRO）的普萘洛尔处理的大鼠和用于增强血管生成的去铁胺处理的大鼠。缺损手术后5或10天，从腹主动脉注射氧化锆-琼脂糖造影剂。然后切出缺陷区域，用17。图1和18所示。1 keV，用于减影CT，分别位于氧化锆k边缘的正下方和正上方。重建图像被分割成骨骼和血管。术后5天，DFO组新生血管体积分数显著高于C组，而PRO组仅倾向于高于C组。两种处理在此阶段对骨再生均无影响。术后10 d，三组新生血管进展程度相似，但DFO组新生骨体积分数明显高于C组，PRO组新生骨体积分数仅高于C组。β-肾上腺素能受体阻滞剂的有效浓度和选择性有待进一步研究。