丙戊酸对大鼠急性脊髓损伤后BDNF及NT-3表达的影响

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12h皮下注射VPA 300mg/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.%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 neurofunc-tional recovery after spinal cord injury through inducing high expression of BDNF and NT-3.