丙戊酸钠充填导管促进大鼠外周神经再生的实验研究

Enhancing nerve regeneration by tubes filled with valproic acid on peripheral nerve defect rats

目的观察丙戊酸钠（VPA）充填导管对缺损外周神经再生的促进作用。方法通过建立大鼠坐骨神经缺损模型，用硅胶管（1cm）进行缺损神经段（0．8cm）的桥接。局部应用8％VPA注射液10μl，观察VPA对神经再生和运动神经功能恢复的影响。30只大鼠随机分成2组，实验组在硅胶管局部注射VPA注射液；对照组在硅胶管局部注入生理盐水。结果术后每只大鼠每2周进行坐骨神经功能指数（SFI）检测，每4周做电生理检查，最后术后12周处死所有大鼠，对坐骨神经进行组织形态学分析。用数字图像分析软件检测有髓神经纤维髓鞘厚度，并对再生神经纤维轴突计数。通过统计软件分析发现SFI，电生理检查，神经组织性形态上两组差异均有统计学意义（P〈0．05）。结论局部使用VPA于神经缺损的大鼠，可以促进损伤神经的轴突再生和运动功能恢复。因此VPA有望在临床上应用于外周神经损伤病例的治疗。

Objective To observe enhancing effect of nerve regeneration on peripheral nerve defect models bridged by silicone tube filled with valproic acid （VPA）. Methods In present research we demonstrate the effect of VPA on peripheral nerve regeneration and recovery of motor function following sciatic nerve transaction in rats. An 8-mm sciatic nerve deficit was created in a rat mode land bridged by a 1-cm silicone tube.Then, 10 μl of 8% VPA were perfused into the silicone chamber in the VPA group. The same volume of normal saline was delivered in the control group. Results Each animal was observed sciatic nerve function index （SFI） at 2-week intervals and studied electrophysiology at 4-week intervals for 12 weeks. Histological and morphometrieal analyses were performed at the end of the experiment, 12 weeks after operation. Using the digital image-analysis system, thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. There was a significant difference in SFI, electrophysiological index （motor-nerve conduct velocity, MCV）, and morphometrical results （regenerated axon number and thickness of myelin sheath） in nerve regeneration between the VPA group and controls （P 〈 0.05 ）. Conclusion The results demonstrated that VPA is able to enhance sciatic nerve regeneration in rats, suggesting the potential clinical application of VPA for the treatment of peripheral nerve injury in humans.