文化大學機構典藏 CCUR:Item 987654321/22929
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    题名: Deciphering the neuroprotective mechanisms of Bu-yang Huan-wu decoction by an integrative neurofunctional and genomic approach in ischemic stroke mice
    作者: Wang, Hsei-Wei
    Liou, Kuo-Tong
    Wang, Yea-Hwey
    Lu, Chung-Kuang
    Lin, Yun-Lian
    Lee, I-Jung
    Huang, Sheng-Teng
    Tsai, Yuan-Hau
    Cheng, Yi-Chieh
    Lin, Hung-Jui
    Shen, Yuh-Chiang
    贡献者: 國術系
    关键词: ACCUMULATION
    FOCAL CEREBRAL-ISCHEMIA
    KAPPA-B
    NEURONAL INJURY
    INFARCT VOLUME
    BRAIN-INJURY
    ACTIVATION
    RATS
    日期: 2011-10-31
    上传时间: 2012-09-06 14:09:48 (UTC+8)
    摘要: Ethnopharmacological relevance: Bu-yang Huan-wu decoction (BHD) is a famous traditional Chinese medicine formula that has been used clinically in Asia to treat stroke-induced disability for centuries, but the underlying neuroprotective mechanisms are not fully understood.

    Aim of the study: In this study, we aim to investigate the mechanisms of action using an integrative neurofunctional and broad genomics approach.

    Materials and methods: Male ICR mice were subjected to an acute ischemic stroke by inducing a middle cerebral ischemic/reperfusion (CI/R) injury. To examine whether BHD could extend the lifespan of mice with a stroke, we used oral administration of BHD (0.5 and 1.0 g/kg) twice daily starting from 2h after ischemia and compared this with vehicle control treatments, recombinant tissue-type plasminogen activator (rt-PA, 10 mg/kg, iv.), and MK-801 (0.2 mg/kg, i.p.). An integrative neurofunctional and genomic approach was performed to elucidate the underlying molecular mechanisms of BHD.

    Results: More than 80% of the mice died within 2 days after stroke induction in the vehicle control treatment group. However, the survival rates and life-spans of mice treated with BHD, rt-PA and MK-801 were significantly enhanced as compared to the vehicle-treated CI/R group in all three cases. Mice treated with BHD (1.0 g/kg) showed the greatest protective effect across all groups. BHD successfully restored brain function, ameliorated the cerebral infarction, and significantly improved the neurological deficits of the mice with a stroke. BHD also reduced inflammation, oxidative stress, and apoptosis, as well as improved neurogenesis. The molecular impacts of BHD were assessed by genome-wide transcriptome analysis using brains from the CUR mice. The results showed a total of 377 ischemia-induced probe-sets that were significantly influenced by BHD including 93 probe-sets that were commonly more abundant in BHD-treated and sham mice, and another 284 ischemia-induced probe sets that were suppressed by BHD. Mining the functional modules and genetic networks of these 377 genes revealed a significant upregulation of neuroprotective genes associated with neurogenesis (6 genes) and nervous system development (9 genes), and a significant down-regulation of destructive genes associated with the induction of inflammation (14 genes), apoptosis (15 genes), angiogenesis (11 genes) and blood coagulation (7 genes) by BHD.

    Conclusions: Our results suggested that BHD is able to protect mice against stroke and extend lifespan primarily through a significant down-regulation of genes involved in inflammation, apoptosis, angiogenesis and blood coagulation, as well as an up-regulation of genes mediating neurogenesis and nervous system development. The changes in expression after treatment with BHD are beneficial after ischemic stroke. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
    關聯: JOURNAL OF ETHNOPHARMACOLOGY Volume: 138 Issue: 1 Pages: 22-33
    显示于类别:[技擊運動暨國術學系] 期刊論文

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