Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling
Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling
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DOI：
10.1016/j.brainresbull.2015.11.019
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发表时间：
2016-03-01
影响因子：
3.8
通讯作者：
Luo, Tianyou
中科院分区：
文献类型：
--
作者：
Miao, Yanping;Zhao, Sheng;Luo, Tianyou
姜黄素（CCM）对脑缺血/再灌注损伤的影响尚不清楚。本研究的目的是调查 CCM 是否减轻脑缺血/再灌注损伤大鼠模型中的炎症和线粒体功能障碍，以及 Sirt1 是否参与这些潜在的保护作用。 Sirtinol 是一种 Sirt1 抑制剂，用于阐明其潜在机制。对大鼠进行 2 小时短暂大脑中动脉闭塞 (MCAO)，然后再灌注 24 小时。脑磁共振成像（MRI）用于检测梗塞体积。还评估了神经学评分和脑含水量。使用商业酶联免疫吸附测定（ELISA）试剂盒检测脑中肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）的水平。通过蛋白质印迹法测量 SIRT1、乙酰化 p53 (Ac-p53)、Bcl-2 和 Bax 的表达。我们的结果表明，CCM 发挥了神经保护作用，如减少梗塞体积和脑水肿以及改善神经系统评分所示。 CCM 还具有抗炎作用，大脑中 TNF-α 和 IL-6 水平的降低表明了这一点。 CCM 升高线粒体膜电位、线粒体复合物 I 活性和线粒体细胞色素 c 水平，但降低胞浆细胞色素 c 水平。此外，CCM 上调 SIRT1 和 Bcl-2 表达，下调 Ac-p53 和 Bax 表达。 CCM 的这些作用被 Sirtinol 消除了。总之，我们的结果表明，CCM 治疗可通过激活 SIRT1 减轻缺血性中风引起的脑损伤。 (C) 2015 Elsevier Inc. 保留所有权利。
The effects of curcumin (CCM) on cerebral ischemia/reperfusion injury are not well understood. The aim of this study was to investigate whether CCM attenuates inflammation and mitochondrial dysfunction in a rat model of cerebral ischemia/reperfusion injury and whether Sirt1 is involved in these potential protective effects. Sirtinol, a Sirt1 inhibitor, was used to elucidate the underlying mechanism. Rats were subjected to 2 h of transient middle cerebral artery occlusion (MCAO), followed by reperfusion for 24 h. Brain magnetic resonance imaging (MRI) was used to detect infarct volumes. Neurological scores and brain water content were also assessed. Levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the brain were detected using commercial enzyme-linked immunosorbent assay (ELISA) kits. Expression of SIRT1, acetylated p53 (Ac-p53), Bcl-2, and Bax was measured by western blotting. Our results suggested that CCM exerted a neuroprotective effect, as shown by reduced infarct volumes and brain edema and improved neurological scores. CCM also exerted anti-inflammatory effects, as indicated by decreased TNF-alpha and IL-6 levels in the brain. CCM elevated mitochondrial membrane potential, mitochondrial complex I activity, and mitochondrial cytochrome c levels, but reduced cytosolic cytochrome c levels. Moreover, CCM upregulated SIRT1 and Bcl-2 expression and downregulated Ac-p53 and Bax expression. These effects of CCM were abolished by sirtinol. In conclusion, our results demonstrate that CCM treatment attenuates ischemic stroke-induced brain injury via activation of SIRT1. (C) 2015 Elsevier Inc. All rights reserved.