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篇名
穿心蓮乙素 (andrographolide) 經由抑制iNOS和gp91phox/NADPH oxidase 2 (NOX2) 的表現保護缺血型中風大鼠腦組織
並列篇名
Neuroprotective Effect of Andrographolide Against Ischemic Stroke in Rats through Reducing iNOS and gp91□/NOX2 Expression
作者 侯毓昌王雅惠劉國同沈郁強
中文摘要
穿心蓮乙素(andrographolide)曾被報導具有抗發炎細胞(嗜中性白血球及微膠細胞)活化作用,但其對中樞神經系統的保護作用並不清楚。本研究以大鼠腦部缺血再灌流(ischemic/reperfusion,CI/R)引發腦中風(ischemic stroke)模式探討穿心蓮乙素之中樞保護作用。大鼠中風後1小時投予穿心蓮乙素(5-10 μg/kg, i.v.),並於中風後24小時評估,可以依劑量相關的方式減少腦梗塞區域 (infarction),並顯著改善大鼠之運動神經行為能力(neurologicaldeficits);中風鼠腦部主要病理生化指標如自由基(ROS)、硝化蛋白質(nitrotyrosine)也都顯著被穿心蓮乙素抑制。中風也造成病理因子iNOS、gp91phox/NADPH oxidase 2(NOX2)及IL-1β大量表現,且與轉錄因子NF-κB及HIF-1α之大量表現平行,而這些現象都可因投予穿心蓮乙素而顯著下降;因此我們推測穿心蓮乙素可經由抑制NF-κB及HIF-1α兩轉錄因子的活化減少中風造成的大量自由基、iNOS、NOX2及IL-1β表現,達到中樞神經保護效果,因此穿心蓮乙素應有潛力發展成為治療缺血型中風的神經保護藥物。Andrographolide, an active component isolated from Andrographis paniculata, has been reported to exhibit anti-inflammatory effects in neutrophils and microglial cells, but its effects on central nervous system (CNS) are unclear. In this study, we explored the CNS protective effect of andrographolide in an ischemic stroke animal model. We performed a cerebral ischemic/reperfusion (CI/R) injury in rats to study whether treatment of andrographolide (5-10 μg/kg, i.v.) 1 h after ischemia could protect rats against stroke. Treatment with andrographolide dose-dependently ameliorated CI/R-induced brain infarction (reduced by 32%~51%) and improved neurological deficits in rats at day 1 after stroke. Elevated pathophysiological markers including reactive oxygen species (ROS) production and protein nitrosylation were significantly reduced by andrographolide. CI/R dramatically enhanced expression of inducible nitric oxide synthase (iNOS), gp91phox/NADPH oxidase 2 (NOX2) and interleukin-1β (IL-1β) that paralleled to the activation of nuclear factor-kappa B (NF-κB) and hypoxia-inducing factor 1-alpha (HIF-1α), and all were significantly diminished by andrographolide. Andrographolide compromises CI/R induced expression of iNOS and gp91phox/NOX2 through impairing NF-κB and HIF-1α activation that confers it as a potential ischemic stroke therapeutic agent.
起訖頁 85-98
關鍵詞 腦中風針灸推拿StrokeAcupunctureChinese manipulation
刊名 中醫藥雜誌  
期數 201012 (21:3-4期)
出版單位 國立中國醫藥研究所
該期刊-上一篇 血紅密孔菌菌絲體之抗發炎活性成分研究
該期刊-下一篇 古今中醫對肝纖維化治療觀點之探討
 

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