基础医学与临床 ›› 2010, Vol. 30 ›› Issue (11): 1138-1142.

• 研究论文 • 上一篇    下一篇

新型化合物FLZ抑制血管性痴呆模型大鼠脑内低氧诱导因子过表达

葛文頔 马波 李伟 郭亮 张建军   

  1. 中国医学科学院北京协和医学院药物研究所 中国医学科学院北京协和医学院药物研究所
  • 收稿日期:2010-08-24 修回日期:2010-09-13 出版日期:2010-11-05 发布日期:2010-11-05
  • 通讯作者: 张建军

Novel compound FLZ inhibits HIF-1α over-expression in rats vascular dementia

Wen-di GE, Bo MA, Wei LI, Liang GUO, Jian-jun ZHANG   

  1. nstitute of Material Medical, CAMS & PUMC Institute of Material Medical, CAMS & PUMC
  • Received:2010-08-24 Revised:2010-09-13 Online:2010-11-05 Published:2010-11-05
  • Contact: Jian-jun ZHANG

摘要: 目的 研究FLZ对暂时性大脑中动脉阻断(tMCAO)局部脑缺血再灌注致血管性痴呆模型大鼠学习记忆能力的作用,及对低氧诱导因子(HIF-1α)表达的影响。方法 用tMCAO缺血2 h再灌致痴呆模型大鼠,30天后用Morris水迷宫实验检测学习记忆能力。用TTC染色检测脑梗塞体积;HE染色检测皮层、海马病理学改变。此外,大鼠tMCAO缺血2 h再灌24 h后用Western blot法检测HIF-1α表达。结果 FLZ明显缩短tMCAO大鼠在Morris水迷宫中的逃避潜伏期,显著减小脑梗塞体积和减轻皮层、海马的病理学改变。FLZ显著抑制缺血2 h时HIF-1α过度表达。结论 FLZ可以显著改善tMCAO诱导的大鼠学习记忆功能障碍,抑制皮层HIF-1α过度表达和神经保护作用可能是其作用机制之一。

关键词: FLZ, 血管性痴呆, 中动脉阻断, 缺氧诱导因子

Abstract: Objective To study the effect of FLZ on the learning and memory ability in vascular dementia rats induced by transient middle cerebral artery occlusion (tMCAO) and its influence on the expression of HIF-1α. Methods tMCAO for 2 hours-induced vascular dementia rats was utilized. The Morris water maze was used to evaluate the learning and memory ability after 30 days of administration. The TTC staining was used to evaluate the infarct volume. The alterations in cortex and hippocampus morphology were assessed by HE staining. In addition, an animal model of tMCAO for 2 hours followed by 24 hours reperfusion was used. The Western blot was used to detect the expression of HIF-1α after 24 hours of reperfusion. Results In the Morris water maze, FLZ administered orally for 30 days reduced remarkably the escape latency time, decreased significantly the infarct volume and also ameliorated the neuropathological alterations in rat cortex and hippocampus. Additionally, FLZ inhibited significantly HIF-1α overexpression induced by tMCAO for 2 hours. Conclusion FLZ could improve significantly memory deficit in vascular dementia rats, its protective effect was related to inhibiting HIF-1α overexpression possibly.

Key words: FLZ, vascular dementia, tMCAO, hypoxia inducible factor-1α