中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (19): 1733-1742.doi: 10.3969/j.issn.1673-5374.2013.19.001

• 原著:脑损伤修复保护与再生 •    下一篇

芹菜籽提取物左旋丁苯酞治疗血管性痴呆：与激活Akt激酶通路有关？

  

  • 收稿日期:2013-03-08 修回日期:2013-05-27 出版日期:2013-07-05 发布日期:2013-07-05

L-3-n-butylphthalide protects against vascular dementia via activation of the Akt kinase pathway

Yaping Huai1, Yanhong Dong2, Jing Xu1, Nan Meng1, Chunfeng Song3, Wenbin Li4, Peiyuan Lv1, 2   

  1. 1 Department of Neurology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
    2 Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
    3 Electron Microscope Center, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
    4 Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
  • Received:2013-03-08 Revised:2013-05-27 Online:2013-07-05 Published:2013-07-05
  • Contact: Peiyuan Lv, M.D., Professor, Chief physician, Doctoral supervisor, Department of Neurology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China; Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China, peiyuanlu@163.com.
  • About author:Yaping Huai, M.D., Associate professor, Associate chief physician
  • Supported by:

    国家自然科学基金（81241037），河北省自然科学基金（H2013307046）

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摘要：

芹菜籽提取物丁苯酞是目前中国的新型抗脑缺血药物，目前已被国家食品药品监督管理局批准为治疗急性缺血性脑卒中的一类新药。临床上左旋丁苯酞治疗急性缺血性脑卒中疗效显著，并且活化的Akt激酶通路可在脑卒中后阻止神经细胞死亡从而提供神经保护作用。实验以此设想左旋丁苯酞对血管性痴呆也有一定的治疗效果，且作用机制在于活化Akt激酶通路。实验采用脑反复缺血再灌注法建立血管性痴呆小鼠模型，于造模前7 d用左旋丁苯酞灌胃，每日1次，共7 d，设为预防性应用组。于造模后第2天给予左旋丁苯酞灌胃，每日1次，共28 d，设为治疗性应用组。Morris水迷宫实验结果发现，造模4周后，预防性应用和治疗性应用左旋丁苯酞均可改善血管性痴呆小鼠的学习记忆缺陷，且以预防性应用左旋丁苯酞效果显著。硫堇染色和Western blot检测结果显示，预防性应用和治疗性应用左旋丁苯酞可减少血管性痴呆小鼠海马CA1区神经细胞数量的丢失，减轻细胞损伤程度，并可伴随海马区磷酸化Akt蛋白表达增多。说明左旋丁苯酞对血管性痴呆具有防治作用，其机制可能通过上调海马中的磷酸化Akt蛋白的表达实现的。

关键词:  神经再生, 脑损伤, 缺血再灌注, Akt, 磷酸化Akt, 水迷宫, 认知功能, 左旋丁苯酞, 海马, 学习, 记忆, 痴呆, 基金资助文章

Abstract:

As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed ex-tract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that l-3-n- butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cere-bral repetitive ischemia/reperfusion, and intragastrically administered l-3-n-butylphthalide daily for 28 consecutive days after ischemia/reperfusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of l-3-n-butylphthalide, especially pretreatment with l-3-n- butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of l-3-n-butylphthalide can reduce loss of pyrami-dal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular demen-tia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after l-3-n- butylphthalide treatment. Experimental findings demonstrate that l-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.

Key words: neural regeneration, brain injury, ischemia/reperfusion, Akt, phosphorylated Akt, Morris water maze, cog-nitive function, 3-n-butylphthalide, hippocampus, learning, memory, dementia, grants-supported paper, neuroregeneration