Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia
Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia
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姜黄素上调转录因子 Nrf2、HO-1 表达并保护大鼠大脑免受局灶性缺血
DOI：
10.1016/j.brainres.2009.05.009
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发表时间：
2009-07-28
期刊：
影响因子：
2.9
通讯作者：
Liu, Ying
中科院分区：
文献类型：
--
作者：
Yang, Chenhui;Zhang, Xiangjian;Liu, Ying
背景：氧化和细胞毒性损伤在脑缺血发病机制中起重要作用，并可能成为治疗的靶点。姜黄素具有抗氧化、抗炎等多种生物学作用。但其背后的机制却知之甚少。转录因子核因子红细胞2相关因子2（Nrf 2）协调自由基清除、外源性物质解毒和氧化还原电位维持所需基因的表达。本研究旨在探讨Nrf 2、HO-1在脑缺血中的时程表达规律及姜黄素在脑缺血中的作用及其可能机制。方法：雄性Sprague-Dawley大鼠，通过右侧MCA阻塞进行永久性局灶性脑缺血。实验一：观察脑缺血后6个时间点Nrf 2和HO-1的表达。实验二检测姜黄素对脑缺血的神经保护作用。在24小时神经功能缺损评估使用一个修改的六点量表;脑含水量的测量;梗死面积分析与2，3，5-三苯基氯化四氮唑（TTC）。采用免疫组化、RT-PCR、Western blot和共聚焦显微镜检测Nrf 2和HO-1的表达。结果如下：与假手术组相比，缺血组Nrf 2和HO-1在基因和蛋白水平均表达上调，并于MCAO后3 h开始上调，24 h达高峰（P
Background: Oxidative and cytotoxic damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Curcumin is proved to elicit a vanity of biological effects through its antioxidant and anti-inflammatory properties. But the mechanisms underlying are poorly understood. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates expression of genes required for free radical scavenging, detoxification of xenobiotics, and maintenance of redox potential. This study evaluated the time course expression regularity of Nrf2, HO-1 and the curcumin's role in cerebral ischemia and its potential mechanism. Methods: Male, Sprague-Dawley rats were subjected to permanent focal cerebral ischemia by right MCA occlusion. Experiment I was used to evaluate the expression of Nrf2 and HO-1 in the cerebral ischemia, 6 time points was included. Experiment 2 was used to detect curcumin's neuroprotection in cerebral ischemia. At 24 h neurological deficit was evaluated using a modified six point scale; brain water content was measured; infarct size was analysed with 2, 3, 5-triphenyltetrazolium chloride (TTC). Immunohistochemistry, RT-PCR, Western blot, and confocal microscope were used to analyse the expression of Nrf2 and HO-1. Results: Compared with sham-operated, Nrf2 and HO-1 were upregulated at gene and protein level in ischemic brain, beginning at 3 h and peaking at 24 h after MCAO (P