Kodavanti Urmila P, Schladweiler Mette C, Gilmour Peter S, Wallenborn J Grace, Mandavilli Bhaskar S, Ledbetter Allen D, Christiani David C, Runge Marschall S, Karoly Edward D, Costa Daniel L, Peddada Shyamal, Jaskot Richard, Richards Judy H, Thomas Ronald, Madamanchi Nageswara R, Nyska Abraham
National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27710, USA.
Environ Health Perspect. 2008 Jan;116(1):13-20. doi: 10.1289/ehp.10379.
Exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity; however, causative components are unknown. Zinc is a major element detected at high levels in urban air.
We investigated the role of PM-associated zinc in cardiac injury.
We repeatedly exposed 12- to 14-week-old male Wistar Kyoto rats intratracheally (1x/week for 8 or 16 weeks) to a) saline (control); b) PM having no soluble zinc (Mount St. Helens ash, MSH); or c) whole-combustion PM suspension containing 14.5 microg/mg of water-soluble zinc at high dose (PM-HD) and d ) low dose (PM-LD), e) the aqueous fraction of this suspension (14.5 microg/mg of soluble zinc) (PM-L), or f ) zinc sulfate (rats exposed for 8 weeks received double the concentration of all PM components of rats exposed for 16 weeks).
Pulmonary inflammation was apparent in all exposure groups when compared with saline (8 weeks > 16 weeks). PM with or without zinc, or with zinc alone caused small increases in focal subepicardial inflammation, degeneration, and fibrosis. Lesions were not detected in controls at 8 weeks but were noted at 16 weeks. We analyzed mitochondrial DNA damage using quantitative polymerase chain reaction and found that all groups except MSH caused varying degrees of damage relative to control. Total cardiac aconitase activity was inhibited in rats receiving soluble zinc. Expression array analysis of heart tissue revealed modest changes in mRNA for genes involved in signaling, ion channels function, oxidative stress, mitochondrial fatty acid metabolism, and cell cycle regulation in zinc but not in MSH-exposed rats.
These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects.
接触颗粒物（PM）与心血管疾病发病率增加有关；然而，致病成分尚不清楚。锌是城市空气中检测到的主要元素。
我们研究了与PM相关的锌在心脏损伤中的作用。
我们对12至14周龄的雄性Wistar Kyoto大鼠进行气管内反复暴露（每周1次，持续8或16周），暴露于以下物质：a）生理盐水（对照）；b）不含可溶性锌的PM（圣海伦火山灰，MSH）；c）高剂量（PM-HD）含14.5微克/毫克水溶性锌的全燃烧PM悬浮液和d）低剂量（PM-LD），e）该悬浮液的水相部分（14.5微克/毫克可溶性锌）（PM-L），或f）硫酸锌（暴露8周的大鼠接受的所有PM成分浓度是暴露16周大鼠的两倍）。
与生理盐水组相比，所有暴露组均出现肺部炎症（8周>16周）。含锌或不含锌的PM，或单独的锌导致局灶性心外膜下炎症、变性和纤维化略有增加。对照组在8周时未检测到病变，但在16周时发现。我们使用定量聚合酶链反应分析线粒体DNA损伤，发现除MSH组外，所有组相对于对照组均造成了不同程度的损伤。接受可溶性锌的大鼠心脏总乌头酸酶活性受到抑制。心脏组织的表达阵列分析显示，在锌暴露但不是MSH暴露的大鼠中，参与信号传导、离子通道功能、氧化应激、线粒体脂肪酸代谢和细胞周期调节的基因的mRNA有适度变化。
这些结果表明，与水溶性PM相关的锌可能是参与PM心脏效应的致病成分之一。
