Ito Tsuyoshi, Suzuki Tadao, Tamura Kumiko, Nezu Toyohiko, Honda Katsuya, Kobayashi Takahiro
Energy and Environment Research Division, Japan Automobile Research Institute, 2530 Karima, Tsukuba, Ibaraki 305-0822, Japan.
Toxicology. 2008 Jan 20;243(3):271-83. doi: 10.1016/j.tox.2007.10.013. Epub 2007 Oct 25.
Epidemiological studies have suggested that fine particulate matter (f-PM) is associated with adverse effects on cardiovascular health. However, these effects on the cardiovascular system have not yet been fully elucidated. Using mRNA expression and correlation analyses, we designed the present study to elucidate (1) translocation of chemicals in inhaled f-PM to the heart, (2) induction of oxidative stress, one of the causes of cardiovascular diseases (CVDs), (3) mRNA expression related to CVDs, and (4) correlations among mRNA expression of various molecules and cardiovascular function. Wistar Kyoto male rats were exposed to concentrated ambient particles (CAPs, 0.6-1.5mg/m3) in Yokohama for 4 days (4.5h/day) or to filtered air for 3 days and CAPs for 1 day or to filtered air for 4 days. Messenger RNA expression and cardiovascular function were measured after the 4-day exposure. In samples of heart tissue, the mRNAs of cytochrome P450 (CYP) 1B1, a biomarker of exposure to chemicals; heme oxygenase-1 (HO-1), a marker of oxidative stress; and endothelin A (ET A) receptor, a receptor of vasoconstrictors, were up-regulated by CAPs; their levels were significantly correlated with the cumulative weight of CAPs in the exposure chamber. The up-regulation of ET A receptor mRNA was significantly correlated with the increase in HO-1 mRNA and weakly with the increase in mean blood pressure (Delta MBP). These results suggest the possibility that chemicals in CAPs might be translocated to the heart, where they induce oxidative stress and activate endothelin signaling, resulting in an increase in the blood pressure. The exposure to f-PM might thus affect cardiovascular function through activation of endothelin signaling.
流行病学研究表明，细颗粒物（f-PM）与心血管健康的不良影响有关。然而，这些对心血管系统的影响尚未完全阐明。本研究通过mRNA表达和相关性分析，旨在阐明：（1）吸入的f-PM中的化学物质向心脏的转运；（2）氧化应激的诱导，氧化应激是心血管疾病（CVD）的病因之一；（3）与CVD相关的mRNA表达；（4）各种分子的mRNA表达与心血管功能之间的相关性。将Wistar Kyoto雄性大鼠暴露于横滨的浓缩环境颗粒物（CAPs，0.6-1.5mg/m3）中4天（每天4.5小时），或暴露于过滤空气中3天，再暴露于CAPs中1天，或暴露于过滤空气中4天。在4天暴露后测量mRNA表达和心血管功能。在心脏组织样本中，细胞色素P450（CYP）1B1（一种化学物质暴露的生物标志物）、血红素加氧酶-1（HO-1，一种氧化应激标志物）和内皮素A（ET A）受体（一种血管收缩剂受体）的mRNA被CAPs上调；它们的水平与暴露室内CAPs的累积重量显著相关。ET A受体mRNA的上调与HO-1 mRNA的增加显著相关，与平均血压升高（ΔMBP）呈弱相关。这些结果表明，CAPs中的化学物质可能转运至心脏，在那里诱导氧化应激并激活内皮素信号传导，导致血压升高。因此，暴露于f-PM可能通过激活内皮素信号传导影响心血管功能。
