双嘧达莫对血管性痴呆大鼠模型学习记忆功能的影响

李国樑,张聪,陈凌云,汤冲,蒋薇,陆丰荣,杨雪梅

中国药学杂志 ›› 2018, Vol. 53 ›› Issue (9) : 695-700.

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中国药学杂志
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中国药学杂志 ›› 2018, Vol. 53 ›› Issue (9) : 695-700. DOI: 10.11669/cpj.2018.09.007
论著

双嘧达莫对血管性痴呆大鼠模型学习记忆功能的影响

  • 李国樑1,张聪2,陈凌云3,汤冲3,蒋薇3,陆丰荣1,杨雪梅3
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Effects of Dipyridamole on Learning and Memory Impairment in Rat with Vascular Dementia

  • LI Guo-liang1, ZHANG Cong2, CHEN Ling-yun3, TANG Chong3, JIANG Wei3, LU Feng-rong1, YANG Xue-mei3
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摘要

目的 建立血管性痴呆(VD)大鼠模型,研究双嘧达莫对VD大鼠学习记忆功能的影响及可能的作用机制。方法 Wistar大鼠采用四血管阻断法(4-VO)制作VD动物模型,采用Morris水迷宫实验和明暗箱穿梭实验测试大鼠的学习记忆能力,分别采用Western-blot法和RT-PCR法检测大鼠海马CA1区核因子(NF)-κB, 肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β蛋白及mRNA表达的变化。结果 VD大鼠经双嘧达莫治疗后,中、高剂量组大鼠在Morris水迷宫到达平台的潜伏期显著减少,目标象限的停留时间和穿越次数显著增加;进入电击箱的潜伏期明显延长;且双嘧达莫给药组能够显著降低大鼠海马CA1区炎症因子NF-κB, TNF-α和IL-1β mRNA的水平和蛋白质的表达。结论 双嘧达莫能够改善VD大鼠的学习记忆损伤,其机制可能缓解大鼠海马CA1区过度的炎症反应相关。

Abstract

OBJECTIVE To investigate the protective effects of dipyridamole on learning and memory impairment of vascular dementia (VD) in rats and explore the potential mechanisms.METHODS 4-Vessel occlusion (4-VO) was performed to establish the model of VD. Spatial memory performance was examined using the Morris water maze and step-through passive avoidance tests. The mRNA and protein levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF-α) and interleukin (IL)-1β were measured by RT-PCR and Western-blot in the CA1 district of hippocampus, respectively.RESULTS Compared with vehicle-treated controls, rats treated with 4-VO spented a longer time finding the hidden platform during the acquisition trials of the Morris water maze task; this was reversed by repeated treatment with dipyridamole. In the passive avoidance test, the model rats showed decreased retention tested 24 h after initial training; this was reversed by dipyridamole. The expression of NF-κB, TNF-α and IL-1β levels were increased after 4-VO performed and the dipyridamole significantly reduced the release of these inflammation-related factors.CONCLUSION Dipyridamole could reverse the learning and memory impairment of VD by reducing the inflammation reaction.

关键词

血管性痴呆 / 双嘧达莫 / 学习记忆损伤 / 炎症反应

Key words

vascular dementia / dipyridamole / learning and memory impairment / inflammatory

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李国樑,张聪,陈凌云,汤冲,蒋薇,陆丰荣,杨雪梅. 双嘧达莫对血管性痴呆大鼠模型学习记忆功能的影响[J]. 中国药学杂志, 2018, 53(9): 695-700 https://doi.org/10.11669/cpj.2018.09.007
LI Guo-liang, ZHANG Cong, CHEN Ling-yun, TANG Chong, JIANG Wei, LU Feng-rong, YANG Xue-mei. Effects of Dipyridamole on Learning and Memory Impairment in Rat with Vascular Dementia[J]. Chinese Pharmaceutical Journal, 2018, 53(9): 695-700 https://doi.org/10.11669/cpj.2018.09.007
中图分类号： R965   

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基金

广东省医学科学技术研究基金资助项目 (A2016557), 广东省职业病防治重点实验室课题(2017B030314152)
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