丙戊酸对大鼠急性脊髓损伤的保护作用

The protective effects of valproic acid on acute spinal cord injury in rats

目的:探讨丙戊酸对脊髓损伤后神经细胞凋亡和热休克蛋白70(HSP70)表达的影响。方法:44只雄性SD大鼠随机分为3组:假手术组(C组)、损伤组(SCI组)和丙戊酸保护组(VPA组)。采用改良的Allen法制作脊髓损伤动物模型。于损伤后第6、24、48、72小时取材。利用BBB评分标准进行不同时段的行为学评分,通过TUNEL法、免疫组化法等观察各组大鼠脊髓损伤后神经细胞凋亡和HSP70表达的变化。结果:VPA组的BBB评分与SCI组相比,在损伤后第48小时和第72小时显著增高(P<0.01)。SCI组和VPA组均出现大量神经细胞凋亡和HSP70阳性表达,VPA组各时间点凋亡指数均明显低于SCI组(P<0.05),而HSP70表达VPA组均明显高于SCI组(P<0.05)。结论:丙戊酸通过减少神经细胞凋亡和诱导HSP70表达,对脊髓损伤起到保护作用。

Objective：To investigate the effects of valproic acid（VPA） on apoptosis of neural cells and expression of heat shock protein 70（HSP70） after acute spinal cord injury（SCI） in rats. Method：Forty-four adult rats were randomly divided into three groups： sham operation group, SCI group and VPA treated group. SCI model was made by modified Allen technique. The rats were sacrificed at the 6thh, 24thh, 48thh, 72ndh after injury. The recovery of locomotor function after injury was evaluated with Basso,Beattie and Bresnahan（BBB） scale. Apoptotic cells were examined by TUNEL method and the expression of HSP70 was detected with immunohistochemistry. Result：The BBB scores were significantly higher in VPA treated group than that in SCI group at the 48thh, 72ndh. Both TUNEL-positive cells and the expression of HSP70 could be seen in SCI group and VPA treated group. Compared with SCI group, in VPA treated group the TUNEL-positive cells decreased significantly, while the expression of HSP70 elevated significantly at the 6thh, 24thh, 48thh, 72ndh after SCI（P0.05）. Conclusion： VPA could exert neuroprotection effect through attenuating apoptosis of neural cells and inducing high expression of HSP70.