依达拉奉对血管性痴呆大鼠海马突触可塑性的影响

Effects of edaravone on synaptic plasticity in hippocampus neurons of vascular dementia rat

目的:探讨依达拉奉(edaravone,Eda)对血管性痴呆(vascular dementia,VD)大鼠海马CA1区神经元突触可塑性的调节作用及分子机制。方法:成年雄性SD大鼠30只,随机分成3组:假手术组、VD组、VD+Eda组,每组10只。应用Morris水迷宫(Morris water maze,M W M)测试各组大鼠的空间认知功能。MWM后,分别记录每只大鼠海马CA1区神经元长时程增强(long-term potentiation,LTP)并进行分析比较;电生理记录后,大鼠断头取脑,制备脑冰冻切片,免疫组织化学测定海马CA1区神经生长相关蛋白-43(G AP-43)的表达情况。结果:VD组大鼠有明显的空间认知障碍;Eda治疗后,VD+Eda组大鼠的空间认知障碍得到显著改善。VD+Eda组兴奋性突触后电位(excitatory postsynaptic potential,EPSP)斜率增加百分比显著高于VD组(P<0.05)。VD组GAP-43的表达量显著低于假手术组(P<0.01),VD+Eda组GAP-43的表达量显著高于VD组(P<0.05)。结论:依达拉奉可通过提高VD大鼠海马CA1区的突触可塑性改善空间认知障碍,其机制与依达拉奉上调VD大鼠海马CA1区GAP-43的表达有关。

Objective： To investigate the effect of edaravone（Eda） on synaptic plasticity in hippocampus neurons of vascular dementia（VD） rat, and explore the molecular mechanisms. Methods： Thirty male Sprague-Dawley rats were randomly divided into 3 groups, which were sham group（n=10）, VD group（n=10） and VD ＋ Eda group（n=10）. The spatial cognition was measured by Morris water maze（MWM） test. The long-term potentiation（LTP） in hippocampal CA1 area was recorded and further compared after MWM. After the electrophysiological experiment, all rats were killed and their brains were isolated respectively. The expression of growth associated protein（GAP-43） in CA1 area of each rat was analyzed by immunohistochemical staining. Results： VD rats showed significant spatial cognitive impairment and the cognitive disorders has been significantly improved by edaravone treatment in VD＋Eda group. The average percentage of EPSP slope increasing in VD＋Eda group was increased markedly compared with that in VD group（P〈0.05）. For the expression of GAP-43 in the CA1 region of hippocampus in VD group, it was lower than that in sham group（P〈0.01） as well as in VD＋Eda group（P〈0.05）. Conclusion： Edaravone could improve the LTP in CA1 hippocampal area of VD rats. The underlying mechanism was associated with its promotion effect on the expression of GAP-43 in the CA1 region.