Villarreal-Calderon Rodolfo, Reed William, Palacios-Moreno Juan, Keefe Sheyla, Herritt Lou, Brooks Diane, Torres-Jardón Ricardo, Calderón-Garcidueñas Lilian
Department of Biomedical and Pharmaceutical Sciences, College of Health Professions and Biomedical Sciences, The University of Montana, Missoula, MT 59812, USA.
Exp Toxicol Pathol. 2012 May;64(4):297-306. doi: 10.1016/j.etp.2010.09.002. Epub 2010 Oct 6.
Air pollution is a serious environmental problem. Elderly subjects show increased cardiac morbidity and mortality associated with air pollution exposure. Mexico City (MC) residents are chronically exposed to high concentrations of fine particulate matter (PM(2.5)) and PM-associated lipopolysaccharides (PM-LPS). To test the hypothesis that chronic exposure to urban pollution produces myocardial inflammation, female Balb-c mice age 4 weeks were exposed for 16 months to two distinctly different polluted areas within MC: southwest (SW) and northwest (NW). SW mice were given either no treatment or chocolate 2g/9.5 mg polyphenols/3 times per week. Results were compared to mice kept in clean air. Key inflammatory mediator genes: cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the LPS receptor CD14 (cluster of differentiation antigen 14) were measured by real-time polymerase chain reaction. Also explored were target NFκB (nuclear factor κB), oxidative stress and antioxidant defense genes. TNF-α, IL-6, and COX-2 were significantly increased in both NW and SWMC mice (p=0.0001). CD14 was up-regulated in SW mice in keeping with the high exposures to particulate matter associated endotoxin. Chocolate administration resulted in a significant down-regulation of TNF-α (p<0.0001), IL-6 (p=0.01), and IL-1β (p=0.02). The up-regulation of antioxidant enzymes and the down-regulation of potent oxidases, toll-like receptors, and pro-apoptotic signaling genes completed the protective profile. Exposure to air pollution produces up-regulation of inflammatory myocardial genes and endotoxin plays a key role in the inflammatory response. Regular consumption of dark chocolate may reduce myocardial inflammation and have cardioprotective properties in the setting of air pollution exposures.
空气污染是一个严重的环境问题。老年受试者显示出与空气污染暴露相关的心脏发病率和死亡率增加。墨西哥城(MC)居民长期暴露于高浓度的细颗粒物(PM(2.5))和与PM相关的脂多糖(PM-LPS)中。为了验证长期暴露于城市污染会导致心肌炎症这一假设,将4周龄的雌性Balb-c小鼠在MC内两个截然不同的污染区域:西南部(SW)和西北部(NW)暴露16个月。SW组小鼠要么不接受治疗,要么每周给予2克含9.5毫克多酚的巧克力,共3次。将结果与饲养在清洁空气中的小鼠进行比较。通过实时聚合酶链反应测量关键炎症介质基因:环氧化酶-2(COX-2)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α),以及LPS受体CD14(分化抗原簇14)。还探究了靶标核因子κB(NFκB)、氧化应激和抗氧化防御基因。NW和SWMC小鼠的TNF-α、IL-6和COX-2均显著增加(p = 0.0001)。SW小鼠的CD14上调,这与高暴露于颗粒物相关内毒素一致。给予巧克力导致TNF-α(p < 0.0001)、IL-6(p = 0.01)和IL-1β(p = 0.02)显著下调。抗氧化酶的上调以及强效氧化酶、Toll样受体和促凋亡信号基因的下调完善了保护作用。暴露于空气污染会导致炎症性心肌基因上调,内毒素在炎症反应中起关键作用。经常食用黑巧克力可能会减轻心肌炎症,并在空气污染暴露的情况下具有心脏保护作用。