Lee James C, Bhora Faiz, Sun Jing, Cheng Guanjun, Arguiri Evguenia, Solomides Charalambos C, Chatterjee Shampa, Christofidou-Solomidou Melpo
Department of Medicine, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L255-65. doi: 10.1152/ajplung.00138.2007. Epub 2007 Dec 14.
Dietary flaxseed (FS) is a nutritional whole grain with high contents of omega-3 fatty acids and lignans with anti-inflammatory and antioxidant properties. We evaluated FS in a murine model of pulmonary ischemia-reperfusion injury (IRI) by dietary supplementation of 0% (control) or 10% (treatment) FS before IRI. Mice fed 0% FS undergoing IRI had a significant decrease in arterial oxygenation (Pa(O(2))) and a significant increase in bronchoalveolar lavage (BAL) protein compared with sham-operated mice. However, mice fed 10% FS undergoing IRI had a significant improvement in both Pa(O(2)) and BAL protein compared with mice fed 0% FS undergoing IRI. In addition, oxidative lung damage was decreased in 10% FS-supplemented mice undergoing IRI, as assessed by malondialdehyde levels. Immunohistochemical staining of lungs for iPF(2alpha)-III F(2) isoprostane, a measure of lipid oxidation, was diminished. FS-supplemented mice had less reactive oxygen species (ROS) release from the vascular endothelium in lungs in an ex vivo model of IRI, and alveolar macrophages isolated from FS-fed mice had significantly reduced ROS generation in response to oxidative burst. Pulmonary microvascular endothelial cells produced less ROS in a flow cessation model of ischemia when preincubated with purified FS lignan metabolites. Pharmacological inhibition of heme oxygenase-1 (HO-1) resulted in only a partial reduction of FS protection in the same model. We conclude that dietary FS is protective against IRI in an experimental murine model and that FS affects ROS generation and ROS detoxification via pathways not limited to upregulation of antioxidant enzymes such as HO-1.
膳食亚麻籽（FS）是一种营养丰富的全谷物，富含具有抗炎和抗氧化特性的ω-3脂肪酸和木脂素。我们通过在肺缺血再灌注损伤（IRI）之前膳食补充0%（对照）或10%（处理）的FS，在小鼠IRI模型中评估了FS。与假手术小鼠相比，接受IRI且喂食0%FS的小鼠动脉氧合（Pa(O₂)）显著降低，支气管肺泡灌洗（BAL）蛋白显著增加。然而，与接受IRI且喂食0%FS的小鼠相比，接受IRI且喂食10%FS的小鼠在Pa(O₂)和BAL蛋白方面均有显著改善。此外，通过丙二醛水平评估，在接受IRI且补充10%FS的小鼠中，肺氧化损伤有所减轻。对肺进行免疫组织化学染色检测iPF(₂α)-III F₂异前列腺素（一种脂质氧化指标），其水平降低。在IRI的体外模型中，补充FS的小鼠肺血管内皮释放的活性氧（ROS）较少，并且从喂食FS的小鼠分离出的肺泡巨噬细胞在氧化爆发时ROS生成显著减少。当用纯化的FS木脂素代谢产物预孵育时，肺微血管内皮细胞在缺血的血流停止模型中产生的ROS较少。在同一模型中，血红素加氧酶-1（HO-1）的药理学抑制仅部分降低了FS的保护作用。我们得出结论，膳食FS在实验性小鼠模型中对IRI具有保护作用，并且FS通过不限于上调抗氧化酶如HO-1的途径影响ROS生成和ROS解毒。
