Jia Gongwei, Tan Botao, Ma Jingxi, Zhang Lina, Jin Xinhao, Li Changqing
Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
Biomed Res Int. 2017;2017:6597401. doi: 10.1155/2017/6597401. Epub 2017 May 17.
The role of Peroxiredoxin 6 (Prdx6) in brain ischemia remains unclear. Curcumin (Cur) treatment elicits neuroprotective effects against cerebral ischemic injury, and the associated mechanisms may involve Prdx6. In this study, we investigated whether Prdx6 and the transcription factor specific protein 1 (SP1) were involved in the antioxidant effect of Cur after stoke.
Focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 2 hours in male Sprague-Dawley rats treated with or without Prdx6 siRNA. Expression of Prdx6 in the penumbra was assessed by Real-Time PCR (RT-PCR), Western blot analysis, and immunoflourescent staining. In addition, infarct volume, neurological deficit score, and oxidative stress were evaluated. Prdx6 levels were also determined in the presence and absence of SP1 antagonist mithramycin A (MTM-A).
Cur treatment upregulated Prdx6 protein expression and the number of Prdx6-positive neuronal cells 24 hours after reperfusion. Cur treatment also attenuated oxidative stress and induced neuroprotective effects against ischemic damage, whereas the beneficial effects of Cur treatment were lost in animals treated with Prdx6-siRNA. Prdx6 upregulation by Cur treatment was abolished by SP1 antagonists MTM.
Prdx6 upregulation by Cur treatment attenuates ischemic oxidative damage through SP1 induction in rats after stroke. This represents a novel mechanism of Cur-induced neuroprotection against cerebral ischemia.
过氧化物酶6（Prdx6）在脑缺血中的作用尚不清楚。姜黄素（Cur）治疗可对脑缺血损伤产生神经保护作用，其相关机制可能涉及Prdx6。在本研究中，我们调查了Prdx6和转录因子特异性蛋白1（SP1）是否参与中风后Cur的抗氧化作用。
在接受或未接受Prdx6 siRNA治疗的雄性Sprague-Dawley大鼠中，通过短暂大脑中动脉闭塞2小时诱导局灶性脑缺血损伤。通过实时聚合酶链反应（RT-PCR）、蛋白质免疫印迹分析和免疫荧光染色评估半暗带中Prdx6的表达。此外，评估梗死体积、神经功能缺损评分和氧化应激。在存在和不存在SP1拮抗剂光神霉素A（MTM-A）的情况下也测定了Prdx6水平。
Cur治疗在再灌注后24小时上调了Prdx6蛋白表达和Prdx6阳性神经元细胞数量。Cur治疗还减轻了氧化应激，并对缺血损伤产生了神经保护作用，而在用Prdx6-siRNA治疗的动物中，Cur治疗的有益作用丧失。Cur治疗引起的Prdx6上调被SP1拮抗剂MTM消除。
Cur治疗上调Prdx6可通过诱导SP1减轻中风后大鼠的缺血性氧化损伤。这代表了Cur诱导的针对脑缺血的神经保护作用的新机制。
