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学科主题: 基础医学
题名:
Early inhibition of HIF-1 alpha with small interfering RNA reduces ischemic-reperfused brain injury in rats
作者: Chen, Chunhua1,4; Hu, Qin1; Yan, Junhao1; Yang, Xiaomei1; Shi, Xianzhong1; Lei, Jiliang1; Chen, Lin2; Huang, Hongyun2; Han, Jingyan3; Zhang, John H.4; Zhou, Changman1,2,3
关键词: Apoptosis ; HIF-1 alpha ; MCAO ; siRNA
刊名: NEUROBIOLOGY OF DISEASE
发表日期: 2009-03-01
DOI: 10.1016/j.nbd.2008.12.010
卷: 33, 期:3, 页:509-517
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: HYPOXIA-INDUCIBLE FACTOR ; CEREBRAL-ARTERY OCCLUSION ; FACTOR-I HIF-1 ; HYPERBARIC-OXYGEN ; APOPTOTIC GENES ; FOCAL ISCHEMIA ; MODEL ; EXPRESSION ; FACTOR-1-ALPHA ; INDUCTION
英文摘要:

Hypoxia-inducible factor-1 (HIF-1) plays an essential role in cerebral ischemia as a proapoptotic factor. We hypothesized that HIF-1 alpha siRNA can protect the brain from ischemic damage by inhibiting HIF-1 alpha induced apoptotic pathway at the RNA level in a rat focal ischemic model. Results showed that treatment with HIF-1 alpha siRNA reduced the infarct volume, decreased mortality, improved neurological deficits and reduced Evans blue extravasation. The expression of HIF-1 alpha mRNA (Real-Time PCR) and protein were significantly silenced and the immunohistochemistry and Western blot revealed the suppression of HIF-1 alpha, VEGF, p53 and Caspase-3. Double fluorescence labeling showed HIF-1 alpha positive immunoreactive materials were partly colocalized with NeuN, p53 and Caspase-3 in the injured cerebral cortex. This study showed that HIF-1 alpha siRNA may protect the ischemic-reperfused neurons in vivo via inhibition of HIF-1 alpha, its downstream VEGF and other apoptotic-related proteins such as p53 and Caspase-3 and may have potentials for the early treatment of ischemic cerebral stroke. (C) 2008 Published by Elsevier Inc.

语种: 英语
所属项目编号: 30672157 ; 20050001123
项目资助者: National Natural Science Foundation of China ; Graduate Student Foundation of China
WOS记录号: WOS:000263748800021
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54505
Appears in Collections:基础医学院_北大医学部天士力微循环研究中心_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Anat & Embryol, Beijing 100083, Peoples R China
2.Beijing Hongtianji Neurosci Acad, Dept Neurosurg, Beijing 100144, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Tasly Microcirculat Res Ctr, Beijing 100083, Peoples R China
4.Loma Linda Univ, Dept Neurosurg, Loma Linda, CA 92350 USA

Recommended Citation:
Chen, Chunhua,Hu, Qin,Yan, Junhao,et al. Early inhibition of HIF-1 alpha with small interfering RNA reduces ischemic-reperfused brain injury in rats[J]. NEUROBIOLOGY OF DISEASE,2009,33(3):509-517.
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