Differential gene expression associated with inflammation and blood pressure regulation induced by concentrated ambient particle exposure
Differential gene expression associated with inflammation and blood pressure regulation induced by concentrated ambient particle exposure
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DOI：
10.3109/08958378.2011.625058
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发表时间：
2011-12-01
影响因子：
2.1
通讯作者：
Ishihara, Yoko
中科院分区：
文献类型：
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作者：
Hasegawa, Go;Hirano, Masato;Ishihara, Yoko
流行病学研究表明，接触颗粒物（PM）会增加呼吸系统和心血管疾病发病率和死亡率的风险。建议小于2.5 μ m的空气动力学直径（PM2.5）的PM可能有助于这些响应。然而，其分子机制仍不清楚。为了阐明在分子水平上的变化，我们研究了基因表达谱的集中环境颗粒物（CAPs）暴露大鼠。将老年F344大鼠暴露于CAP（594 μ g/m3）或清洁空气中，每天4小时，持续3天，然后切除肺和心脏组织用于DNA微阵列分析。与炎症和血压调节相关的表达谱揭示了肺中7个基因和心室中3个基因的差异表达。根据补体激活相关基因，补体因子B（Bf），补体成分2和4a（C4 a），和C1抑制剂基因在CAP暴露大鼠肺上调。Bf和C4 a基因在心脏中也上调。这表明当需要激活补体级联反应时，治疗的动物准备好产生这些蛋白质。促炎细胞因子白细胞介素-1 β在CAP暴露的大鼠肺中也上调。与血压调节相关的基因（血管紧张素I转换酶）也在CAPs暴露的大鼠肺中上调。在CAPs暴露的大鼠心脏中，血压负调节因子（神经肽Y）下调。这些结果表明，CAPs暴露早期可能通过激活炎症反应和破坏血压调节而影响呼吸和心血管器官。
Epidemiological studies have indicated that exposure to particle matter (PM) increased the risk of respiratory and cardiovascular morbidity and mortality. It is suggested that PM smaller than 2.5 mu m in aerodynamic diameter (PM2.5) may contribute to these responses. However, the molecular mechanism is still unknown. To elucidate the changes in molecular level, we investigated the gene expression profile of concentrated ambient particles (CAPs)-exposed rats. Aged F344 rats were exposed with CAPs (594 mu g/m(3)) or clean air 4 h per day for 3 days, and lung and heart tissues were then excised for DNA microarray analysis. Expression profiles related to inflammation and blood pressure regulation revealed differential expression of 7 genes in the lung and that of 3 genes in the heart ventricle. According to the complement activation-associated genes, complement factor B (Bf), complement component 2 and 4a (C4a), and C1 inhibitor genes were up-regulated in CAPs-exposed rat lung. Bf and C4a genes were also up-regulated in the heart. These suggest the treated animal ready for production of these proteins when activation of complement cascade is required. Pro-inflammatory cytokine, interleukin-1 beta, was also up-regulated in CAPs-exposed rat lung. Gene related with blood pressure regulation (angiotensin I converting enzyme) was also up-regulated in CAPs-exposed rat lung. Negative regulator of blood pressure (neuropeptide Y) was down-regulated in CAPs-exposed rat heart. These results indicate that CAPs may affect respiratory and cardiovascular organs by activation of inflammatory responses and disintegration of blood pressure regulation in early stage of CAPs exposure.