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[米拉丁减轻慢性脑灌注不足大鼠的白质损伤和认知障碍]

[Militarine alleviates white matter damage and cognitive impairment in rats with chronic cerebral hypoperfusion].

作者信息

Wang Yao, Zhao Xiang-yu, Li Xin-ya, Li Shuai, Zhang Jian-jun

出版信息

Yao Xue Xue Bao. 2016 May;51(5):738-42.

Abstract

Chronic cerebral hypoperfusion is a model for white matter lesions (WMLs) and cognitive impairment. In this study, we used the model in testing the protective effect of (-)-(2R)-1-[(4-β-D-glucopyranosyloxy)benzyl]-4-[4-(β-D-glucopyranosyloxy)benzyl]-2-isobutyl malate (militarine) on the white matter damaged. The model was established by bilateral common carotid ligation. Militarine (10 and 20 mg·kg(-1)·d(-1)) or saline was intragastrically administered daily for 30 days following the operation. Militarine (20 mg·kg-1·d-1)-treated rats exhibited significantly shorter escape latency, latency of the first time crossing and more numbers of platform crossings in Morris water maze task. Luxol fast blue (LFB) staining and Western blot analysis indicated that militarine promoted rehabilitation of white matter and increased levels of myelin basic protein (MBP) in the rats. Immunohistochemical staining for 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase) revealed that militarine (20 mg·kg(-1)·d(-1)) markedly suppressed loss of CNPase-positive oligodendrocytes in the rat model. In conclusion, militarine can improve WMLs and cognitive impairment in the rat chronic hypoperfusion model.

摘要

慢性脑灌注不足是白质病变(WMLs)和认知障碍的一种模型。在本研究中,我们使用该模型来测试(-)-(2R)-1-[(4-β-D-吡喃葡萄糖氧基)苄基]-4-[4-(β-D-吡喃葡萄糖氧基)苄基]-2-异丁基苹果酸(水苏碱)对受损白质的保护作用。该模型通过双侧颈总动脉结扎建立。术后每天灌胃给予水苏碱(10和20 mg·kg⁻¹·d⁻¹)或生理盐水,持续30天。在莫里斯水迷宫任务中,接受水苏碱(20 mg·kg⁻¹·d⁻¹)治疗的大鼠表现出明显缩短的逃避潜伏期、首次穿越潜伏期和更多的平台穿越次数。Luxol固蓝(LFB)染色和蛋白质免疫印迹分析表明,水苏碱促进了大鼠白质的修复并提高了髓鞘碱性蛋白(MBP)的水平。对2',3'-环核苷酸3'-磷酸二酯酶(CNPase)的免疫组织化学染色显示,水苏碱(20 mg·kg⁻¹·d⁻¹)显著抑制了大鼠模型中CNPase阳性少突胶质细胞的丢失。总之,水苏碱可以改善大鼠慢性灌注不足模型中的白质病变和认知障碍。

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