丙戊酸对大鼠急性脊髓损伤后BDNF及NT-3表达的影响|大鼠脊髓损伤模型

　　[摘要] 目的 探讨丙戊酸（VPA）对脊髓损伤后脑源性神经营养因子（BDNF）和神经营养素3（NT-3）表达的影响。 方法 将60只雄性SD大鼠随机分为三组：对照组（C组）、损伤组（SCI组）和丙戊酸保护组（VPA组）。采用改良Allen法制作脊髓损伤动物模型。VPA组术后即刻及其后每12 h皮下注射VPA 300 mg/kg；C组和SCI组在相应时间点注射等体积的生理盐水。于伤后24、48、72 h和1周取材。利用BBB评分标准进行不同时段的行为学评分。通过免疫组化法观察各组大鼠脊髓损伤后BDNF及NT-3表达的变化。 结果 BBB评分显示，C组运动功能未受影响，VPA组的BBB评分均高于SCI组，在伤后48、72 h和1周两者比较，差异有统计学意义（P < 0.05）。与C组比较，SCI组和VPA组的BDNF及NT-3表达在各时间点均明显增加（P < 0.05），但VPA组各时间点的BDNF及NT-3表达均明显高于SCI组（P < 0.05）。 结论 VPA可促进大鼠脊髓损伤后神经功能恢复，其机制可能与促进BDNF及NT-3表达有关。
　　[关键词] 脊髓损伤；丙戊酸；脑源性神经营养因子；神经营养素3
　　[中图分类号] R651.2 [文献标识码] A [文章编号] 1673-7210（2012）07（c）-0023-03
　　Effects of valproic acid on the expression of BDNF and NT-3 in rats after acute spinal cord injury
　　LI Xinzhi
　　Department of Anatomy and Histo-Embryology, Chengdu Medical College, Sichuang Province, Chengdu 610083, China
　　[Abstract] Objective To investigate the effects of valproic acid (VPA) on the expression of BDNF and NT-3 in rats after acute spinal cord injury. Methods 60 adult rats were randomly divided into three groups: control group (C group), spinal cord injury group (SCI group) and VPA treatment group (VPA group). Spinal cord injury model was made by modified Allen technique. VPA (300 mg/kg) was administrated in rats through subcutaneous injection immediately after injury and repeated per 12h after injury, while C group and SCI group were received the same dose of normal saline injection at the same time point. The rats were killed at 24, 48, 72 h and 1 week after injury. The behavior scores were evaluated with BBB scale at each time point after injury. The expression of BDNF and NT-3 were detected by immunohistochemistry method. Results The BBB score indicated that motor function in the C group was normal, and the scores of the VPA group were significantly higher than those of the SCI group at 48, 72 h and 1 week after injury, the differences were statistically significant (P < 0.05). Compared with C group, the expression of BDNF and NT-3 both increased obviously at each time point after injury in the VPA group and SCI group (P < 0.05), however, compared with the SCI group, the expression of BDNF and NT-3 evidently increased in the VPA group at each time point after injury (P < 0.05). Conclusion VPA can promote neurofunctional recovery after spinal cord injury through inducing high expression of BDNF and NT-3.
　　[Key words] Spinal cord injury; Valproic acid; Brain derived neurotrophic factor; Neurotrophin-3
　　脊髓损伤（spinal cord injury， SCI）后由于神经元无法再生以及继发性损伤，造成运动和感觉功能障碍，严重影响患者生活质量，迄今为止尚无切实有效的治疗方法。近年来研究表明，丙戊酸（valproic acid，VPA）具有多方面的神经营养效应和神经保护作用[1]，而有关VPA对SCI的影响及机制的报道很少。研究证实，脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）和神经营养素3（neurotrophin-3，NT-3）具有阻止神经元死亡和促进轴突再生的双重作用[2]。本研究通过探讨VPA对大鼠SCI后BDNF和NT-3表达的影响，为临床治疗SCI提供新方向。