摘要
背景转录因子NF-E2相关因子2(Nf-E2 related factor-2,Nrf2)抗氧化反应元件(antioxidant response element,ARE)通路广泛分布于机体心血管系统中,激活后可上调内源性抗氧化系统减轻心肌的氧化损伤。目的阐述Nrf2-ARE通路作为抗心肌缺血,再灌注损伤(ischemigreperfusion injury,VRI)的潜在靶点,并探讨其可能的保护机制。内容Nrf2-ARE通路处于氧化应激、炎症反应的中心地位,介导编码抗氧化蛋白和二项解毒酶基因的基础表达和诱导表达;多种外源性化合物可以激活Nrf2-ARE通路,在转录水平上调节抗氧化蛋白及二项解毒酶基因的表达,增强内源性抗氧化系统的能力从而在减少氧自由基产生、抗炎症反应、减轻钙超载、抗心肌细胞凋亡等方面减轻心肌I/RI。趋向激活Nrf2-ARE通路可为临床抗I/RI提供新的策略。
Background Nf-E2 related factor-2 (Nrf2)-antioxidant response element (ARE) pathway is ubiquitously expressed in the cardiovascular system. Activation of Nrf2-ARE pathway reduces myocardiac ischemia-reperfusion injury through upregulation of endogenous anti-oxidation. Objective To elucidate if Nrf2-ARE pathway is a potential therapeutic target for anti- myocardial ischemia/reperfusion injury (I/RI) and to determine the cardioprotection mechanisms. Content Nrf2-ARE signal pathway plays a key role in cellular defense against oxidative stress and inflammation. It mediatess the basal and inducible expression of battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes. Many exogenous agents activates Nrf2 pathway to enhance cellular antioxidant capacity through the upregulation of endogenous antioxidants and phase 2 enzymes, which reduces reactive oxygen species (ROS) formation, attenuates inflammation, relieves Ca2~ overload, and decreases apoptosis in myocardium. Trend Nrf2-ARE signal pathway is a promising therapeutic target for the treatment of myocardial I/Pal.
出处
《国际麻醉学与复苏杂志》
CAS
2012年第2期103-106,共4页
International Journal of Anesthesiology and Resuscitation
基金
国家自然科学基金(30960366/C160203)