Rhoden Claudia R, Wellenius Gregory A, Ghelfi Elisa, Lawrence Joy, González-Flecha Beatriz
Department of Environmental Health, Physiology Program, Harvard School of Public Health, Boston, MA 02115, USA.
Biochim Biophys Acta. 2005 Oct 10;1725(3):305-13. doi: 10.1016/j.bbagen.2005.05.025. Epub 2005 Jun 20.
Epidemiological studies show that increases in particulate air pollution (PM) are associated with increases in cardiopulmonary morbidity and mortality. However, the mechanism(s) underlying the cardiac effects of PM remain unknown. We used pharmacological strategies to determine whether oxidants are implicated in PM-dependent cardiac dysfunction and whether PM-induced increase in autonomic stimulation on the heart mediates cardiac oxidative stress and toxicity. Adult Sprague-Dawley rats were exposed to either intratracheal instillation of urban air particles (UAP 750 microg) or to inhalation of concentrated ambient particles (CAPs mass concentration 700+/-180 microg/m3) for 5 h. Oxidative stress and cardiac function were evaluated 30 min after UAP instillation or immediately after exposure to CAPs. Instillation of UAP led to significant increases in heart oxidants measured as organ chemiluminescence (UAP: 38+/-5 cps/cm2, sham: 10+/-1 cps/cm2) or thiobarbituric acid reactive substances (TBARS, UAP: 76+/-10, Sham 30+/-6 pmol/mg protein). Heart rate increased immediately after exposure (UAP: 390+/-20 bpm, sham: 350+/-10 bpm) and returned to basal levels over the next 30 min. Heart rate variability (SDNN) was unchanged immediately after exposure, but significantly increased during the recovery phase (UAP: 3.4+/-0.2, Sham: 2.4+/-0.3). To determine the role of ROS in the development of cardiac malfunction, rats were treated with 50 mg/kg N-acetylcysteine (NAC) 1 h prior to UAP instillation or CAPs inhalation. NAC prevented changes in heart rate and SDNN in UAP-exposed rats (340+/-8 and 2.9+/-0.3, respectively). To investigate the role of the autonomic nervous system in PM-induced oxidative stress, rats were given 5 mg/kg atenolol (beta-1 receptor antagonist), 0.30 mg/kg glycopyrrolate (muscarinic receptor antagonist) or saline immediately before exposure to CAPs aerosols. Both atenolol and glycopyrrolate effectively prevented CAPs-induced cardiac oxidative stress (CL(ATEN): 11+/-1 cps/cm2, CL(GLYCO): 10+/-1 cps/cm2, TBARS(ATEN): 40+/-6 pmol/mg protein, TBARS(GLYCO): 38+/-6 pmol/mg protein). These data indicate that PM exposure increases cardiac oxidants via autonomic signals and the resulting oxidative stress is associated with significant functional alterations in the heart.
流行病学研究表明，空气中颗粒物污染（PM）的增加与心肺疾病的发病率和死亡率上升有关。然而，PM对心脏产生影响的潜在机制仍不清楚。我们采用药理学方法来确定氧化剂是否与PM所致的心脏功能障碍有关，以及PM引起的心脏自主神经刺激增加是否介导了心脏氧化应激和毒性作用。将成年Sprague-Dawley大鼠通过气管内滴注城市空气颗粒（UAP 750微克）或吸入浓缩环境颗粒（CAPs质量浓度700±180微克/立方米）暴露5小时。在滴注UAP后30分钟或暴露于CAPs后立即评估氧化应激和心脏功能。滴注UAP导致以器官化学发光（UAP：38±5 cps/cm²，假手术组：10±1 cps/cm²）或硫代巴比妥酸反应性物质（TBARS，UAP：76±10，假手术组30±6 pmol/mg蛋白质）衡量的心脏氧化剂显著增加。暴露后心率立即升高（UAP：390±20次/分钟，假手术组：350±10次/分钟），并在接下来的30分钟内恢复到基础水平。暴露后心率变异性（SDNN）立即无变化，但在恢复阶段显著增加（UAP：3.4±0.2，假手术组：2.4±0.3）。为了确定活性氧在心脏功能障碍发展中的作用，在滴注UAP或吸入CAPs前1小时用50毫克/千克N-乙酰半胱氨酸（NAC）处理大鼠。NAC可预防UAP暴露大鼠的心率和SDNN变化（分别为340±8和2.9±0.3）。为了研究自主神经系统在PM诱导的氧化应激中的作用，在暴露于CAPs气雾剂前立即给大鼠注射5毫克/千克阿替洛尔（β-1受体拮抗剂）、0.30毫克/千克格隆溴铵（毒蕈碱受体拮抗剂）或生理盐水。阿替洛尔和格隆溴铵均有效预防了CAPs诱导的心脏氧化应激（CL(ATEN)：11±1 cps/cm²，CL(GLYCO)：10±1 cps/cm²，TBARS(ATEN)：40±6 pmol/mg蛋白质，TBARS(GLYCO)：38±6 pmol/mg蛋白质）。这些数据表明，暴露于PM可通过自主神经信号增加心脏氧化剂，由此产生的氧化应激与心脏的显著功能改变有关。
