生物谷報(bào)道：一項(xiàng)新的研究顯示，膽固醇與柴油機(jī)廢氣微粒的混合物能夠使動脈硬化,，從而造成心臟病發(fā)作和中風(fēng),。研究人員發(fā)現(xiàn),，如果這兩種因素結(jié)合在一起,，將比僅含有柴油機(jī)微粒的煤煙或膽固醇造成更大的健康危害,。
迄今為止,，柴油機(jī)廢氣——所含微粒的直徑小于2.5微米——與心血管疾病的關(guān)系尚未搞清,。流行病學(xué)證據(jù)曾表明兩者之間存在聯(lián)系,，但研究人員尚無法確定這一機(jī)制,。然而研究顯示,，就像膽固醇的有害形式——低密度脂蛋白（LDL）——一樣，柴油機(jī)微粒能夠?qū)е伦杂苫谘苤嗅尫?，后者是一類氧分子，能夠破壞人體組織,。
在這項(xiàng)新的研究中,，美國加利福尼亞大學(xué)洛杉磯分校的免疫學(xué)家Andre Nel和他的同事將人體血管組織樣本同時(shí)暴露在煤煙、LDL膽固醇或兩者兼有的環(huán)境中,。研究人員發(fā)現(xiàn),，煤煙與LDL膽固醇的混合物尤其善于激活一類基因，后者能夠?qū)е卵苎装Y,，同時(shí)引發(fā)動脈硬化或動脈硬化癥,。
為了驗(yàn)證活體動物體內(nèi)是否存在類似現(xiàn)象，研究人員利用遺傳手段培育了一種實(shí)驗(yàn)室小鼠,，它們具有很高的膽固醇水平,。隨后，這些小鼠被分別放置在3種環(huán)境中,。第一組小鼠在兩個月的時(shí)間里,，生活在過濾后的空氣中；第二組小鼠暴露在具有最細(xì)微顆粒的柴油機(jī)廢氣中,；第三組小鼠則與細(xì)微以及中等大小的柴油機(jī)廢氣微粒為伴,。研究人員通過對這些嚙齒類動物的肺組織進(jìn)行研究后發(fā)現(xiàn),，兩個柴油機(jī)組小鼠與人類組織樣本以及類似基因激活模式的受損程度基本相同。且暴露在最細(xì)微柴油機(jī)廢氣顆粒環(huán)境中的小鼠受傷最重,。研究小組在7月25日出版的《基因組生物學(xué)》雜志上報(bào)告了這一研究成果,。
加利福尼亞大學(xué)舊金山分校的毒物學(xué)家Stanton Glantz表示：“迄今為止，這是第一項(xiàng)探究空氣污染對心血管系統(tǒng)造成影響背后的生物學(xué)機(jī)制的研究,。”他說,，“大多數(shù)人都相信一定發(fā)生了什么，然而這項(xiàng)研究為我們提供了真實(shí)的證據(jù),。”
Nel表示,，在接下來的研究中，他希望搞清抗氧化劑——在某些蔬菜水果中發(fā)現(xiàn)的化合物,，能夠防止自由基的傷害——能否阻止柴油機(jī)廢氣的損傷,。他的研究小組同時(shí)計(jì)劃鑒別使人體對空氣污染更加具有易感性的基因，從而使高危人群能夠通過脫氧核糖核酸（DNA）檢測得以確認(rèn),。（科學(xué)時(shí)報(bào)）
原始出處:
Genome Biology 2007, 8:R149 doi:10.1186/gb-2007-8-7-r149
Published 26 July 2007
Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells
Ke Wei Gong , Wei Zhao , Ning Li , Berenice Barajas , Michael Kleinman , Constantinos Sioutas , Steve Horvath , Aldons J Lusis , Andre Nel and Jesus A Araujo
Abstract (provisional)
Background
Ambient air pollution is associated with increased cardiovascular morbidity and mortality. We have found that exposure to ambient ultrafine particulate matter (PM), highly enriched in redox cycling organic chemicals, promotes atherosclerosis in mice. We hypothesize that these pro-oxidative chemicals could synergize with oxidized lipid components generated in low density lipoprotein (LDL) particles to enhance vascular inflammation and atherosclerosis.
Results
We have used human microvascular endothelial cells (HMEC) to study the combined effects of a model air pollutant, diesel exhaust particles (DEP), and oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (ox-PAPC) on genome-wide gene expression. We treated HMEC in triplicate wells with an organic DEP extract (5 micrograms/ml), ox-PAPC (10, 20 and 40 micrograms/ml) or combination of both compounds for 4 hours. Gene expression profiles were assessed by Illumina microarray technology. Both the DEP extract and ox-PAPC co-regulated a large number of genes. We used network analysis to identify co-expressed gene modules. We found three modules that were most highly enriched in genes that were differentially regulated by the stimuli. These modules were also enriched in synergistically coregulated genes and pathways relevant to vascular inflammation. We validated this synergy in vivo by demonstrating that liver gene expression of hypercholesterolemic mice exposed to ambient ultrafine particles exhibited significant upregulation of the module genes.
Conclusions
Diesel exhaust particles and oxidized phospholipids synergistically affect the expression profile of several gene modules that correspond to pathways relevant to vascular inflammatory processes such as atherosclerosis.
