衰老对硝酸酯类药物引起活性氮介质和活性氧介质增高的影响  

Aging aggravates nitrate-induced reactive oxygen species / reactive nitrogen species changes in human

作　　者：赵东晖[1] 范谦[1] 柳景华[1] 

机构地区：[1]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所心内科,100029

出　　处：《心肺血管病杂志》2014年第6期804-807,共4页Journal of Cardiovascular and Pulmonary Diseases

摘　　要：目的:以往研究显示,硝酸酯类药物和衰老都会引发体内活性氧介质(ROS)和活性氮介质(RNS)的增加,本研究旨在探讨年龄是否会影响硝酸酯类药物的这种促进作用。方法:75例不稳定心绞痛患者,分成32例中年组和43例老年两组。所有患者均给予硝酸酯类药物(50μg/min)48h。在试验开始时和用药48小时时,获取血样标本,对血样中的ROS[丙二醛(MDA),髓过氧化物酶(MPO)和还原性谷胱甘肽(GSH)]和RNS(硝基、亚硝基,NOX;过氧亚硝酸阴离子,ONOO-)]的水平进行检测。结果:硝酸酯类药物的使用,引起中年组血浆MDA水平[用药前(1.22±0.37)nmol/m L,用药后(1.61±0.47)nmol/m L,P<0.05]增加60%;老年组MDA水平[用药前(2.07±0.77)nmol/m L,用药后(4.05±0.80)nmol/m L,P<0.05],增加140%;GSH两组分别减少了9%和48%;硝酸酯类药物使用前,老年组血浆硝基化酪氨酸(398.29±117.0)nmol/L水平为仅为中年组(296.57±120.48)nmol/L的105%,药物使用48h后,老年组血浆硝基化酪氨酸水平(1 182.30±295.01)nmol/L增高到中年组(610.82±217.36)nmol/L,增高210%。结论:在硝酸酯类药物的使用过程中,除了药物本身增加机体内ROS和RNS,年龄增加能够促进硝酸酯类药物的这种作用。Objective： Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species（ROS） and reactive nitrogen species（RNS）. To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS ＇alteration in vivo. Methods： 32 adults and 43 elderly unstable angina （UA） patients were subjected to 48 hours of isosorbide dinitrate intravenous injection （50 μg/minutes） in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress included plasma malondialdehyde （MDA）, myeloperoxidase （MPO）, and reduced glutathione （GSH）. Plasma concentrations of NOx and nitrotyrosine served as markers of RNS. Results ： Nitrates caused MDA level 60% [ pre （ 1.22 ±0. 37 ） nmol/mL, post（ 1.61 ±0. 47 ） nmol/mL, P 〈 0. 051 and 140% [ pre （ 2. 07 ±0. 77 ） nmol/mL, post （ 4. 05 ± 0. 80 ） nmol/mL, P 〈 0. 05] increase in middle age and elder groups respectively. Before nitrate therapy nitrotyrosine level in eider group is 105 % of middle age （ 398.29 ±117.00 ） nmol/L vs. （ 296.57 ± 120.48 ） nmol/L, but after 48h therapy elder group is 210% （ 1 182.30 ± 295.01 ） nmol/L vs. （610. 82 ± 217.36） nmol/L of middle age group. Our study demonstrated nitrate therapy significantly increased in vivo ROS/RNS stress in the elderly compared to adult patients, confirmed by animal data. Conclusion： Taken together, the present study＇ s data suggests a synergism between nitrate treatment and the aging process.

关 键 词：活性氧介质 活性氮介质 过氧亚硝酸阴离子 衰老 

分 类 号：R54[医药卫生—心血管疾病]