In Utero Exposure of Hyperlipidemic Mice to Diesel Exhaust: Lack of Effects on Atherosclerosis in Adult Offspring Fed a Regular Chow Diet.

In Utero Exposure of Hyperlipidemic Mice to Diesel Exhaust: Lack of Effects on Atherosclerosis in Adult Offspring Fed a Regular Chow Diet.
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DOI:
10.1007/s12012-017-9399-x
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发表时间:
2017-10
影响因子:
3.2
通讯作者:
Rosenfeld ME
Rosenfeld ME
中科院分区:
医学4区
文献类型:
--
作者:
Harrigan J;Ravi D;Ricks J;Rosenfeld ME

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子宫压力与晚年代谢性疾病的风险增加有关。在这项研究中,我们研究了子宫内柴油尾气(DE)暴露对遗传性高脂血症小鼠成年动脉粥样硬化易感性的影响。怀孕的载脂蛋白E缺陷小鼠在整个妊娠期间接受DE暴露(~250-300gμg/m3PM2.5,每天6小时,每周5天)或过滤空气(FA)。记录了处理对产仔数和性别分布的影响。分别在8周龄、12周龄和16周龄测定血浆胆固醇和甘油三酯。测定16周龄处死时尿8-异前列腺素和肝脏8-羟基脱氧鸟苷水平。检测抗氧化剂基因血红素加氧酶-1和谷氨酸-半胱氨酸连接酶修饰物及其催化亚基在肺、肝和主动脉中的表达。测量主动脉窦和无名动脉的动脉粥样硬化病变的平均面积和频率。暴露于DE的小鼠的产仔数明显较小,出生后死亡率较高。治疗组之间在血脂或脂蛋白谱、抗氧化剂基因表达或氧化应激标志物方面没有显著差异。DE组和FA组的主动脉窦或无名动脉的平均动脉粥样硬化病变面积也没有显着差异,尽管DE暴露组的病变发生率较高。我们的研究表明,子宫内DE暴露不会影响晚年的脂蛋白代谢、氧化还原动态平衡或发生更大的动脉粥样硬化病变的风险。
Uterine stress is associated with an increased risk of later life metabolic diseases. In this study, we investigated the effect of diesel exhaust (DE) exposure in utero on adult susceptibility to atherosclerosis in genetically hyperlipidemic mice. Pregnant apolipoprotein E-deficient mice received either DE exposure (~250–300 μg/m3 PM2.5 for 6 h/day, 5 days/week) or filtered air (FA) throughout gestation. Treatment effects on litter size and gender distribution were recorded. Plasma cholesterol and triglycerides were measured at 8, 12 and 16 weeks of age. Urinary 8-isoprostane and liver 8-hydroxy-deoxyguanosine levels were measured at killing at 16 weeks of age. Expression of the antioxidant genes heme oxygenase-1 and the glutamate-cysteine ligase modifier and catalytic subunits were measured in the lung, liver and aorta. The average area and frequency of atherosclerotic lesions were measured in the aortic sinus and innominate arteries. There were significantly smaller litters and higher postnatal mortality in the DE-exposed mice. There were no significant differences in plasma lipids or lipoprotein profiles, expression of antioxidant genes or markers of oxidative stress between treatment groups. There were also no significant differences in average atherosclerotic lesion area in the aortic sinus or innominate arteries of the DE and FA groups although there was a higher frequency of lesions in the DE-exposed group. Our study indicates that in utero DE exposure does not influence later life lipoprotein metabolism, redox homeostasis or the risk of developing larger atherosclerotic lesions.
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