Ozone-Induced Vascular Contractility and Pulmonary Injury are Differentially Impacted by Diets Enriched with Coconut Oil, Fish Oil, and Olive Oil

Fish oil, olive oil, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they can protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet enriched with fish, olive, or coconut oil starting at 4 weeks of age for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4h/day for 2 consecutive days. The fish oil diet completely abolished phenylephrine-induced vasoconstriction that was increased following ozone exposure in the animals fed all other diets. Only the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors in the lung. Serum miRNA profile was assessed using small RNA-sequencing in normal and fish oil groups and demonstrated marked depletion of a variety of miRNAs, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that while fish oil offered protection from ozone-induced aortic vasoconstriction, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective dietary supplement.鱼油、橄榄油与椰子油膳食补充剂均具备多种心脏保护益处，但目前尚未明确其能否抵御空气污染引发的不良影响。本研究假设此类膳食补充剂可缓解臭氧诱导的全身与肺部损伤效应。实验选取4周龄的雄性Wistar Kyoto大鼠（Wistar Kyoto rats），将其分为四组，分别饲喂正常饲料，或添加鱼油、橄榄油、椰子油的强化饲料，持续饲喂8周。随后将各组大鼠暴露于空气或浓度为0.8ppm的臭氧中，每日暴露4小时，连续暴露2天。在其余三组饲喂强化饲料的大鼠中，臭氧暴露后苯肾上腺素诱导的血管收缩作用增强，而鱼油饲料组则完全消除了该现象。仅鱼油饲料组可升高支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）中肺损伤与炎症标志物的基础水平。正常饲料组、椰子油饲料组与橄榄油饲料组大鼠的臭氧诱导性肺损伤/炎症程度相当，而鱼油饲料组大鼠的相关标志物表达则出现异常改变。无论是否经过臭氧暴露，鱼油饲料组大鼠的支气管肺泡灌洗液中均出现体积增大的泡沫样巨噬细胞，同时伴随肺部胆固醇转运蛋白、胆固醇受体及核受体的mRNA表达水平下调。通过小RNA测序（small RNA-sequencing）检测正常饲料组与鱼油饲料组大鼠的血清miRNA表达谱，结果显示鱼油组多种miRNA的表达显著下调，其中部分miRNA来源于脾脏，且未观察到臭氧特异性的表达变化。综合上述实验结果可知：尽管鱼油可抵御臭氧诱导的主动脉血管收缩，但同时会加重肺损伤与炎症，且损伤脂质转运机制进而导致泡沫样巨噬细胞堆积，这提示我们需警惕此类血管保护性膳食补充剂可能存在的非靶向肺部效应，这类效应可能抵消其整体获益。