Epidemiological studies have shown that exposure to air pollution particles is associated with cardiovascular diseases, whereas the role in the initiation of atherosclerosis is unresolved. Atherosclerosis is considered to be an inflammatory disease that also involves oxidative stress. Here we investigated effects of oxidative stress elicited by diesel exhaust particles (DEP) in the aorta, liver, and lung of dyslipidemic ApoE(-/-) mice at the age when visual plaques appear in the aorta (11-13 weeks). DEP was administrated by intraperitoneal injection (0, 50, 500 and 5,000 microg DEP/kg bodyweight) in order to omit vascular effects secondary to pulmonary inflammation. The mice were killed either 6 or 24h after the administration. Inflammation was measured as the expression of inducible nitric oxide synthase (iNOS) and serum nitric oxide and DNA damage was measured by the comet assay. The expression of iNOS mRNA was increased in the liver 6h after the administration. The level of oxidized purine bases, determined as formamidopyrimidine DNA glycosylase sites was increased by 67% (95% CI: 11-124%) in the liver after 24h in the mice administrated with only 50 microg/kg bodyweight. However, there was no indication of systemic inflammation determined as the serum concentration of nitric oxide and iNOS expression, and DNA damage was not increased in the aorta. These observations indicate that intraperitoneal DEP injection does not induce inflammation or oxidatively damaged DNA in the lung and aorta, whereas a direct effect in terms of inflammation and oxidized DNA was observed in the liver of dyslipidemic ApoE(-/-) mice.

译文

:流行病学研究表明,暴露于空气污染颗粒与心血管疾病有关,而在引发动脉粥样硬化中的作用尚无定论。动脉粥样硬化被认为​​是还涉及氧化应激的炎性疾病。在这里,我们研究了血脂异常ApoE(-/-)小鼠在主动脉出现斑块的年龄(11-13周)时,柴油机排气颗粒(DEP)在主动脉,肝脏和肺中引起的氧化应激的影响。通过腹膜内注射给予DEP(0、50、500和5,000 microg DEP / kg体重),以消除继发于肺部炎症的血管作用。给药后6或24小时处死小鼠。通过诱导型一氧化氮合酶(iNOS)和血清一氧化氮的表达来测量炎症,并通过彗星试验测量DNA损伤。给药6h后,肝脏中iNOS mRNA的表达增加。仅以50 microg / kg体重给药的小鼠在24小时后,肝脏中被氧化的嘌呤碱基水平(被确定为甲酰嘧啶DNA糖基化酶位点)增加了67%(95%CI:11-124%)。然而,没有根据血清一氧化氮浓度和iNOS表达确定全身炎症的迹象,主动脉中的DNA损伤也没有增加。这些观察结果表明,腹膜内DEP注射不会在肺和主动脉中引起炎症或氧化损伤的DNA,而在血脂异常的ApoE(-/-)小鼠的肝脏中观察到了对炎症和氧化的DNA的直接作用。

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