内皮型一氧化氮合酶脱偶联与氧化应激  

Endothelial Nitric Oxide Synthase Uncoupling And Oxidative Stress

作　　者：张洪平[1] 唐宁[1] 卞卡[1,2,3] 

机构地区：[1]上海中医药大学穆拉德中药现代化研究中心,上海201203 [2]上海教委一氧化氮和炎症医学E-研究院,上海201203 [3]美国德克萨斯大学休斯顿医学院综合生物及药理学系,德克萨斯大学分子医学研究所,美国休斯顿tx77030

出　　处：《辽宁中医药大学学报》2009年第12期36-40,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家科技部"十一五"支撑计划资助项目(2006BAI11B08-03);上海市科委基础研究重点项目(08430711300;08DZ1972104);上海市教委高校一氧化氮与炎症医学E-研究院计划项目(E-04010)

摘　　要：内皮细胞功能障碍是造成许多心脑血管疾病的共同病理基础。NO利用率降低和活性氧(ROS)过量生成是导致内皮功能紊乱的一个重要因素。内皮型一氧化氮合酶脱偶联(eNOS uncoupling)是导致NO水平下降和氧自由基水平升高的重要机制,其中ROS水平升高又是造成eNOS脱偶联的主要原因。随着对ROS病理生理作用认识的不断深入,发现ROS的生物学作用具有两面性,一方面ROS与蛋白质、脂质、核酸等生物大分子反应,引发一些病理过程,另一方面ROS通过不同的信号途径对一些生理过程进行调控。该现象主要是由ROS分布的区域化造成。通过抑制ROS合成特异性关键酶减少特定区域内的具体的ROS减少氧化应激、逆转eNOS脱偶联、进而改善血管内皮功能,为防治心脑血管疾病提开辟新的途径。Endothelial dysfunction is the common pathological base for a number of cardiovascular diseases. Reduction of NO bioavailability and excessive generation of reactive oxygen species （ROS） are key factors which cause endothelial dysfunction. Endothelial nitric oxide synthase uncoupling （eNOS- uncoupling） is an important mechanism underlying the pathological phenomenon of reduced NO production and enhanced free radicals generation. Higher level of ROS is the major cause of eNOS-uncoupling which exerts influence on protein structure, co-factor as well as the substrate of eNOS. Furthermore, the dual effects of ROS also attract the attention： on the one hand, ROS react with biological macromolecules such as proteins, lipids, nucleic acids, which results a number of pathological consequences. On the other hand, ROS is necessary for certain physiological signaling. The compartmental effects of ROS should be responsible for above phenomenon. Inhibition of ROS in specific region may open up novel pathway for the prevention and treatment of cardiovascular diseases through the means of blocking key ROS synthesis enzymes; preventing and reversing eNOS uncoupling, and improving endothelial function.

关 键 词：一氧化氮 信号途径 氧化应激 

分 类 号：R2-03[医药卫生—中医学]