自体肋间神经联合酸性成纤维细胞生长因子移植治疗高位脊髓损伤

背景：酸性成纤维细胞生长因子具有调节细胞增殖、移行、分化和生存的作用，也可以下调已知轴突再生的抑制因子如蛋白聚糖等，帮助轴突克服这些抑制因子，对神经纤维再生有重要作用。 目的：观察酸性成纤维细胞生长因子联合周围神经移植治疗大鼠高位脊髓损伤的可行性及效果。 方法：健康成年雌性SD大鼠108只随机抽签法分为自体神经组、自体神经联合生长因子组、高位脊髓横断组。咬除大鼠T8~10棘突、椎板，显露硬膜囊，水平切断高位脊髓并切除3 mm，显微镜下确认无神经纤维相连。自体神经组、自体神经联合生长因子组取双侧第8~10对肋间神经各2 cm，将肋间神经交叉移植入高位脊髓缺损处(近端白质与远端灰质、远端白质与近端灰质)，分别以纤维蛋白凝胶、含有酸性成纤维细胞生长因子的纤维蛋白凝胶固定植入的肋间神经，缝合硬膜。高位脊髓横断组断端间旷置。术后90 d，行体感诱发电位及运动诱发电位检测观察神经电生理恢复情况。术后76 d，生物素葡聚糖胺顺行神经示踪观察运动传导束恢复情况。术后60 d，后肢BBB运动功能评分观察肢体运动恢复情况。 结果与结论：高位脊髓横断组大鼠均未引出体感及运动诱发电位波形。自体神经组、自体神经联合生长因子组均可引出体感及运动诱发电位，自体神经联合生长因子组体感诱发电位及运动诱发电位的平均潜伏期和波幅、BBB评分均明显优自体神经组(P < 0.01)。自体神经组和自体神经联合生长因子组在损伤区有较多生物素葡聚糖胺标记阳性神经纤维通过，明显多于高位脊髓横断组(P < 0.01)，自体神经联合生长因子组多于自体神经组(P < 0.01)。提示自体周围神经移植酸性成纤维细胞生长因子能更好地恢复高位脊髓损伤后大鼠肢体运动功能。

Autologous intercostal nerve plus acidic fibroblast growth factor transplantation for the treatment of high-level spinal cord injury

BACKGROUND: Acidic fibroblast growth factor can regulate cell proliferation, migration, differentiation and survival, also can down-regulate the known inhibitor of axon regeneration, such as proteoglycan, help axons overcome these inhibitory factors, and have significant role on the regeneration of nerve fibers. OBJECTIVE: To study the feasibility and effect of the acidic fibroblast growth factor combined with peripheral nerve transplantation in the treatment of high-level spinal cord injury in rats. METHODS: A total of adult 108 female SD rats were randomly divided into autologous nerve group, autologous nerve combined with acidic fibroblast growth factor group, and high-level spinal cord injury group. The rat T8-10 spinous process and lamina were bite, revealing dural sac, high-level spinal cord was resected at a horizon level, cutting 3 mm, no nerve fibers were confirmed to be attached under the microscope. In the autogenous nerve group and autologous nerve combined with acidic fibroblast growth factor group, bilateral the 8th to 10th pairs of intercostal nerves were harvested 2 cm, then cross-transplanted into high-level spinal cord defect (proximal white matter and distal gray matter, distal white matter and proximal gray matter), fibrin gel and fibrin gel containing acidic fibroblast growth factor were used respectively to fix the implanted intercostal nerve, followed by dural suture. High-level spinal cord transection group was subjected to exclusion between stumps. At 90 days postoperation, somatosensory evoked potential and motor evoked potential were used to test nerve electrophysiological recovery. At 76 days postoperation, biotinylated dextran amine anterograde tracing was applied to observe the motor conduction bundle recovery. At 60 days postoperation, hindlimb motor function recovery was assessed by BBB score. RESULTS AND CONCLUSION: The somatosensory and motor evoked potential waveforms were not elicited in rats of high-level spinal cord transection group, but did elicit in autogenous nerve group and autologous nerve combined acidic fibroblast growth factor group. The average latency and amplitude of somatosensory and motor evoked potentials, as well as BBB scores in autologous nerve combined acidic fibroblast growth factor group were significantly superior to autologous nerve group (P < 0.01). In the autogenous nerve group and autologous nerve combined acidic fibroblast growth factor group, many more biotinylated dextran amine-positive nerve fibers passed in the damage zone, compared with high-level spinal cord transection group (P < 0.01), the autologous nerve combined acidic fibroblast growth factor group was more than autogenous nerve group (P < 0.01). It is indicated that autologous peripheral nerve graft acidic fibroblast growth factor can better restore the limb motor functions of rats after high-level spinal cord injury.