Valproic acid improves outcome after rodent spinal cord injury: Potential roles of histone deacetylase inhibition
Valproic acid improves outcome after rodent spinal cord injury: Potential roles of histone deacetylase inhibition
复制标题
DOI：
10.1016/j.brainres.2011.03.040
复制
发表时间：
2011-06-17
期刊：
影响因子：
2.9
通讯作者：
Dong, Qiang
中科院分区：
文献类型：
--
作者：
Lv, Lei;Sun, Yan;Dong, Qiang
包括丙戊酸 (VPA) 在内的组蛋白脱乙酰酶 (HDAC) 抑制剂已成为神经系统疾病的一种有前途的治疗干预措施。我们研究了大鼠脊髓损伤 (SCI) 模型中乙酰化组蛋白的水平和 VPA 的治疗潜力。 SCI或假手术后不同时间点（12小时、1天、3天、1周和2周）收集脊髓，评估乙酰化组蛋白H3（Ac-H3）和H4（Ac-H4）的水平。 SCI后立即注射VPA或媒介物1周，观察组蛋白乙酰化、细胞凋亡以及神经行为，以测试VPA的效果。受伤脊髓中的 Ac-H3 和 Ac-H4 水平早在 SCI 后第 1 天就开始显着下降，并在 SCI 后至少 2 周内保持低于未受伤对照的水平。注射VPA可显着阻止Ac-H3和Ac-H4的减少，上调Hsp70和Bcl-2的表达，减少细胞凋亡，最终促进运动恢复。我们的数据表明 SCI 导致组蛋白乙酰化显着减少； VPA在SCI模型中具有神经保护作用，其机制可能涉及HDAC抑制和保护蛋白诱导。 (C) 2011 Elsevier B.V. 保留所有权利。
Histone deacetylases (HDAC) inhibitors including valproic acid (VPA) have emerged as a promising therapeutic intervention in neurological disorders. We investigated the levels of acetylated histone and the therapeutic potential of VPA in a rat model of spinal cord injury (SCI). At different time points (12 h, 1 day, 3 days, 1 week and 2 weeks) after SCI or sham surgery, the spinal cords were collected to evaluate the levels of acetylated histone H3 (Ac-H3) and H4 (Ac-H4). VPA or vehicle was injected for 1 week starting immediately after SCI and histone acetylation, apoptosis, as well as neurobehavior were observed to test the effect of VPA. The levels of Ac-H3 and Ac-H4 in the injured spinal cord started to significantly decrease as early as day 1, and remained below those in uninjured controls for at least 2 weeks after SCI. Injection of VPA markedly prevented the reductions of Ac-H3 and Ac-H4, upregulated the expressions of Hsp70 and Bcl-2, reduced apoptosis and finally promoted locomotion recovery. Our data demonstrated that SCI led to marked reduction in histone acetylation; VPA was neuroprotective in the SCI model, and the mechanism may involve HDAC inhibition and protective proteins induction. (C) 2011 Elsevier B.V. All rights reserved.