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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (6): 39-43.doi: 10.6040/j.issn.1671-7554.0.2014.812

• 基础医学 • 上一篇    下一篇

新型组蛋白脱乙酰酶抑制剂11r对癫痫持续状态大鼠的神经保护作用

乔珊, 韩涛, 李文娜, 王胜军, 赵秀鹤, 杨雪, 刘学伍   

  1. 山东大学齐鲁医院神经内科, 山东 济南 250012
  • 收稿日期:2014-11-11 修回日期:2015-02-23 出版日期:2015-06-10 发布日期:2015-06-10
  • 通讯作者: 刘学伍。E-mail:snlxw1966@163.com E-mail:snlxw1966@163.com
  • 基金资助:
    国家自然科学基金(81171071);山东省自然科学基金(ZR2010HM052)

Neuroprotective effects of histone deacetylases inhibitor 11r on rats following status epilepticus

QIAO Shan, HAN Tao, LI Wenna, WANG Shengjun, ZHAO Xiuhe, YANG Xue, LIU Xuewu   

  1. Department of Neurology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Received:2014-11-11 Revised:2015-02-23 Online:2015-06-10 Published:2015-06-10

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摘要： 目的 探讨新型组蛋白脱乙酰酶(HDACs)抑制剂11r对癫痫导致脑损伤的神经保护作用。方法 将40只Sprague-Dawley大鼠随机平均分为5组:对照组、匹鲁卡品组、治疗Ⅰ组(致痫后腹腔注射11r,2.5 mg/kg,1次/d,连续3 d)、治疗Ⅱ组(致痫后腹腔注射11r,25 mg/kg, 1次/d,连续3 d)、11r预处理组。通过氯化锂-匹鲁卡品诱发癫痫持续状态(SE),观察大鼠的行为学表现。致痫24 h,通过HE染色观察各组大鼠脑组织形态学改变情况。致痫72 h,通过尼氏染色和免疫组化方法观察各组大鼠海马CA1、CA3区神经元存活情况及组蛋白乙酰化水平。结果 与匹鲁卡品组相比,11r预处理组SE发作潜伏期延长且致痫大鼠死亡率降低(P<0.05)。与匹鲁卡品组相比,治疗Ⅰ组及治疗Ⅱ组海马CA1及CA3区神经元变性的程度降低。治疗Ⅰ组及治疗Ⅱ组海马CA1及CA3区的组蛋白乙酰化水平比匹鲁卡品组高(P<0.05),治疗Ⅰ组与治疗Ⅱ组间的差异无统计学意义(P >0.05)。结论 11r可改善氯化锂-匹鲁卡品诱发癫痫持续状态后急性期脑组织的病理变化及组蛋白乙酰化水平,对癫痫所致脑损伤有一定的保护作用。

关键词: 组蛋白乙酰化, 癫痫, 神经保护, 海马, 抗惊厥

Abstract: Objective To investigate the neuroprotective effects of histone deacetylases(HDACs) inhibitor 11r on rats after seizures. Methods A total of 40 rats were randomly divided into 5 groups: control group,pilocarpine group, treatment group I(administered with 11r, 2.5 mg/kg, once a day,intraperitoneally in three consecutive days), treatment group Ⅱ(administered with 11r, 25 mg/kg, once a day, intraperitoneally in three consecutive days), and 11r pretreatment group. Lithium chloride and pilocarpine were used to induce status epilepticus. The behaviors of rats in each group were observed. HE staining was performed to detect neuronal degeneration in hippocampus 24 hours after pilocarpine-induced seizure. At 72 hour after seizures, Nissl staining and immunohistochemical staining were used to evaluate the loss of neurons and histone acetylation levels of hippocampal CA1 and CA3 regions in each group. Results Compared with pilocarpine group, 11r pretreatment group showed delayed pilocarpine-induced seizures and reduced mortality (P<0.05). Compared with those in pilocarpine group, the degrees of neuronal loss and degeneration in both treatment group Ⅰ and Ⅱ reduced (P<0.05), and the levels of histone acetylation in hippocampal CA1 and CA3 regions increased (P<0.05),while, the difference was not statistically significant between treatment group Ⅰ and Ⅱ (P>0.05). Conclusion New HDACs inhibitor 11r can improve pathological changes and histone acetylation levels of the brain in rats in the acute phase of pilocarpine-induced status epilepticus, which exerts neuroprotective effects on rats after seizures.

Key words: Hippocampus, Neuroprotection, Anticonvulsant, Seizures, Histone acetylation

中图分类号: 

  • R742.1
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