Yang Chenhui, Zhang Xiangjian, Fan Hongguang, Liu Ying
Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Brain Res. 2009 Jul 28;1282:133-41. doi: 10.1016/j.brainres.2009.05.009. Epub 2009 May 13.
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.
Male, Sprague-Dawley rats were subjected to permanent focal cerebral ischemia by right MCA occlusion. Experiment 1 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.
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<0.05). Curcumin high dose (100 mg/kg) upregulated Nrf2 and HO-1 in MCAO-affected brain tissue and reduced infarct volume (P<0.05), brain water content (P<0.05) and behavioral deficits (P<0.05) caused by MCAO.
Nrf2 and HO-1 were induced at the early stage after MCAO. Curcumin protected the brain from damage caused by MCAO, this effect may be through upregulation of the transcription factor Nrf2 expression. Nrf2 may be one of the strategic targets for cerebral ischemic therapies.
氧化和细胞毒性损伤在脑缺血发病机制中起重要作用，可能是治疗靶点。姜黄素因其抗氧化和抗炎特性被证明能引发多种生物学效应。但其潜在机制尚不清楚。转录因子核因子E2相关因子2（Nrf2）协调自由基清除、外源性物质解毒和维持氧化还原电位所需基因的表达。本研究评估了Nrf2、HO-1的时间进程表达规律以及姜黄素在脑缺血中的作用及其潜在机制。
雄性Sprague-Dawley大鼠通过右侧大脑中动脉闭塞进行永久性局灶性脑缺血。实验1用于评估脑缺血中Nrf2和HO-1的表达，包括6个时间点。实验2用于检测姜黄素在脑缺血中的神经保护作用。在24小时时，使用改良的六点量表评估神经功能缺损；测量脑含水量；用2,3,5-三苯基四氮唑氯化物（TTC）分析梗死体积。采用免疫组织化学、RT-PCR、Western印迹和共聚焦显微镜分析Nrf2和HO-1的表达。
与假手术组相比，缺血脑中Nrf2和HO-1在基因和蛋白水平上调，在大脑中动脉闭塞后3小时开始，24小时达到峰值（P<0.05）。姜黄素高剂量（100mg/kg）上调大脑中动脉闭塞影响的脑组织中Nrf2和HO-1，并减少大脑中动脉闭塞引起的梗死体积（P<0.05）、脑含水量（P<0.05）和行为缺陷（P<0.05）。
大脑中动脉闭塞后早期诱导Nrf2和HO-1。姜黄素保护大脑免受大脑中动脉闭塞引起的损伤，这种作用可能是通过上调转录因子Nrf2的表达。Nrf2可能是脑缺血治疗的战略靶点之一。
