The Neuroprotection of Oxymatrine in Cerebral Ischemia/Reperfusion Is Related to Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)-Mediated Antioxidant Response: Role of Nrf2 and Hemeoxygenase-1 Expression
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概要
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Cerebral ischemia-reperfusion (CI/R) injury remains a major medical problem due to the lack of effective therapies. Previous studies have shown that increasing the activity of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and gene targets in cell culture and stroke animal models is highly neuroprotective. Oxymatrine is the major quinolizidine alkaloid extracted from the root of Sophora flavescens AIT, and has been proved to be protective after ischemia in recent studies. The present study was designed to investigate the potential effect of oxymatrine in ischemia-reperfusion injury in rats brain and to explore the possible role of oxymatrine in Nrf2 pathway. The results indicated that the ischemic infarct and edema were significantly reduced in rats that received oxymatrine, with a corresponding improvement in neurological function after CI/R. In immunohistochemistry and Western blotting analyses, Nrf2 and hemeoxygenase-1 (HO-1) were up-regulated in ischemic cortex, beginning at 6 h, peaking at 48 h and declining at 72 h after CI/R. Intraperitoneal injection of oxymatrine inhibited the production of lipid peroxidation and increased the activities of Nrf2 and HO-1 in rats brain after CI/R. Taken together, these results suggest that oxymatrine administered systemically protected brain against focal ischemia-reperfusion damage at the early stage of stroke, and that activating Nrf2/HO-1 pathway may contribute to the neuroprotective action of oxymatrine in rat focal brain ischemia-reperfusion model. Thus, treatment of stroke with oxymatrine may prevent severe consequences after brain attack.
著者
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Du Wei
Department Of Internal Medicine Wayne State University School Of Medicine Harper Hospital Detroit Me
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Li Min
Department Of Pathology Peking University Health Science Center
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Cui Lili
Department Of Neurology Xuanwu Hospital Capital University Of Medical Sciences
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Wang Lina
Department Of Urology First Affiliated Hospital Of Dalian Medical University
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Yang Rui
Department of Pharmaceutics, Shenyang Pharmaceutical University
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Zhang Xiangjian
Department of Neurology, Second Hospital of Hebei Medical University
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Liu Lingling
Department of Neurology, Second Hospital of Hebei Medical University
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Li Min
Department Of Chemistry Mississippi State University
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Du Wei
Department of Neurology, Second Hospital of Hebei Medical University
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Wang Lina
Department of Neurology, Second Hospital of Hebei Medical University
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Li Min
Department of Neurology, Second Hospital of Hebei Medical University
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Yang Rui
Department of Neurology, Second Hospital of Hebei Medical University
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Cui Lili
Department of Neurology, Second Hospital of Hebei Medical University
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Wang LiNa
Department of Neurology, Affiliated Xi' an No.9 Hospital, Medical School of Xi'an Jiaotong University
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