脊髓损伤大鼠交感神经活性对骨骼力学特性影响的研究

In addition to the damage of motor and sensory pathway, spinal cord injury (SCI) also disrupt autonomic pathway which control the bone metabolism. Following SCI, skeleton below the level of injury (LOI) develop bone loss rapidly. Several mechanisms contribute to the bone loss after SCI including decreased skeletal mechanical loading due to limb paralysis, altered hormone and change in the autonomic system control, which would eventually result in increased bone resorption. However, there is very little data with respect to the change of bone macromechanics properties following SCI. Most studies regarding the change of skeleton after SCI have focused on the mechanical loading and altered hormone, while SCI also contribute to the abnormality in sympathetic nervous activity below the LOI. Although more attention have been paid to the effect on bone metabolism through the sympathetic nervous system, there is also lack of study about the effect of sympathetic nervous activity on bone mechanical properties following SCI. Accordingly, the aim of this animal model based study is threefold: (1) to obtain the fundamental data regarding the change in bone mechanical properties after SCI; (2) to analyze the essential correlation between the severity of injury and the bone macromechanics properties; (3) to investigate the effect of sympathetic nervous activity on altered bone mechanical properties in complete SCI and its potential mechanism. In addition, the relationship between the change in bone mechanical properties and the catecholamine concentration as well as the osteoclast activity will also be investigated.

脊髓损伤不仅累及传递随意运动和感觉信号的躯体神经通路，还累及负责骨骼代谢的自主神经通路。脊髓损伤后损伤平面以下快速出现骨丢失。多种机制对脊髓损伤后骨丢失起作用，包括肢体活动减少所致的骨骼力学负荷减少、激素改变和自主神经系统调控的变化，最终均会加速骨吸收，但目前尚缺少脊髓损伤后骨骼宏观力学特性改变的相关研究。脊髓损伤所致骨骼变化的研究多着眼于机械负荷和激素改变，而脊髓损伤还会导致损伤平面以下交感神经系统的异常。虽然交感神经系统对骨代谢的作用受到关注，但目前亦无脊髓损伤后交感神经活性对骨骼力学特性影响的研究报道。我们希望通过本实验研究，在大鼠脊髓损伤模型中获得脊髓损伤后骨骼力学特性变化情况的基本数据，分析不同损伤程度与骨骼宏观力学特性的本质关联。并且探讨交感神经活性对完全性脊髓损伤后骨骼力学特性改变的影响和可能的作用机制，以及骨骼力学变化与血儿茶酚胺含量、破骨细胞活性的相关性。

脊髓损伤不仅累及传递随意运动和感觉信号的躯体神经通路，还累及负责骨骼代谢的自主 神经通路。脊髓损伤后损伤平面以下快速出现骨丢失。多种机制对脊髓损伤后骨丢失起作用， 包括肢体活动减少所致的骨骼力学负荷减少、激素改变和自主神经系统调控的变化，最终均会加速骨吸收，但目前尚缺少脊髓损伤后骨骼宏观力学特性改变的相关研究。脊髓损伤所致骨骼变化的研究多着眼于机械负荷和激素改变，而脊髓损伤还会导致损伤平面以下交感神经系统的异常。虽然交感神经系统对骨代谢的作用受到关注，但目前亦无脊髓损伤后交感神经活性对骨骼力学特性影响的研究报道。.本实验研究首先建立大鼠T3脊髓完全性损伤模型，随机分组后，分别给予或不给予结直肠扩张刺激诱发自主神经反射异常，随后采集基于micro-CT的股骨近端及远端、第四腰椎椎体的骨结构参数变化特性的数据，以及成骨与破骨细胞的骨病理学改变，包括HE染色及酒石酸耐药酸性磷酸酶TRAP染色等；测量损伤及诱发自主神经异常后的血压，儿茶酚胺的含量变化，并分析组间交感活性的变化。结果发现，结直肠扩张刺激可诱发脊髓损伤后血压升高，组间差异具有统计学意义；micro-CT显示诱发自主神经反射异常后股骨近端骨密度明显降低；测量损伤后的血浆中CTX-I及OCN的骨代谢指标，发现脊髓损伤后其浓度下降，诱发自主神经异常可使其浓度进一步降低。免疫组化结果提示诱发自主神经反射异常后，破骨细胞活性增强。.本研究结果表明，脊髓损伤后骨丢失与交感活性改变相关，骨骼结构变化与血儿茶酚胺含量、破骨细胞活性具有相关性。由此提示脊髓损伤后交感活性改变在骨重建和骨质疏松的发生中起重要作用，交感活性的异常增加加剧了骨吸收和减少骨形成，最终引起骨丢失。