Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor α in mice
Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor α in mice
复制标题
DOI：
10.1016/j.neulet.2003.09.001
复制
发表时间：
2003-12-11
影响因子：
2.5
通讯作者：
Namura, S
中科院分区：
文献类型：
--
作者：
Inoue, H;Jiang, XF;Namura, S
过氧化物酶体增殖物激活受体（Peroxisome proliferator-activated receptor，PPARs）是一类配体依赖性转录因子，属于核受体家族。我们研究了PPARalpha激动剂和白藜芦醇（葡萄中含有的多酚）是否能保护大脑免受缺血。为了研究白藜芦醇是否激活PPARs，我们使用荧光素酶报告质粒进行了基于细胞的转染活性测定。在原代皮层培养物和血管内皮细胞中，白藜芦醇可激活PPARalpha和PPARgamma。白藜芦醇（20毫克/公斤，3天）减少梗死体积36%，在24小时后，大脑中动脉闭塞野生型小鼠。PPARalpha激动剂非诺贝特（30 mg/kg，3天）和Wy-14643（30 mg/kg，7天）发挥了类似的脑保护作用。然而，白藜芦醇和非诺贝特未能保护PPARalpha基因敲除小鼠的大脑。数据表明，PPARalpha激动剂通过PPARalpha保护大脑。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors which belong to the nuclear receptor family. We examined whether PPARalpha agonists and resveratrol, a polyphenol contained in grapes, protect the brain against ischemia. To investigate whether resveratrol activates PPARs, we performed a cell-based transfection activity assay using luciferase reporter plasmid. PPARalpha and PPARgamma were activated by resveratrol in primary cortical cultures and vascular endothelial cells. Resveratrol (20 mg/kg, 3 days) reduced infarct volume by 36% at 24 h after middle cerebral artery occlusion in wild-type mice. The PPARalpha agonists fenofibrate (30 mg/kg, 3 days) and Wy-14643 (30 mg/kg, 7 days) exerted similar brain protection. However, resveratrol and fenofibrate failed to protect the brain in PPARalpha knockout mice. The data indicate that PPARalpha agonists protect the brain through PPARalpha. (C) 2003 Elsevier Ireland Ltd. All rights reserved.