Okamoto Nami, Murata Takuji, Tamai Hiroshi, Tanaka Hiroyuki, Nagai Hiroichi
Department of Pediatrics, Osaka Medical College, Takatsuki City, Osaka Prefecture, Japan.
Int Arch Allergy Immunol. 2006;141(2):172-80. doi: 10.1159/000094896. Epub 2006 Aug 4.
We investigated the role of antioxidants in airway hyperresponsiveness to acetylcholine using young asthma model mice, which were sensitized and stimulated with ovalbumin.
The mice had been fed either a normal diet, an alpha-tocopherol-supplemented diet or a probucol-supplemented diet 14 days before the first sensitization. They were immunized with antigen at intervals of 12 days and, starting from 10 days after the second immunization, they were exposed to antigen 3 times every 4th day using an ultrasonic nebulizer. Twenty-four hours after the last antigen inhalation, airway responsiveness to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was collected. A blood and lung tissue study was also carried out.
Twenty-four hours after the last antigen challenge, both IL-4 and IL-5 in the BALF of alpha-tocopherol-supplemented mice were significantly decreased. The IL-5 level in probucol-supplemented mice was also decreased, but there was no difference in IL-4 levels. The serum IgE level was decreased in probucol-supplemented mice. Differential cell rates of the fluid revealed a significant decrease in eosinophils due to antioxidant supplementation. Airway hyperresponsiveness to acetylcholine was also repressed in antioxidant-supplemented mice. In histological sections of lung tissue, inflammatory cells and mucus secretion were markedly reduced in antioxidant-supplemented mice. We investigated the antioxidant effect on our model mice by examining 8-isoprostane in BALF and lung tissue, and acrolein in BALF; however, our experiment gave us no evidence of the antioxidant properties of either alpha-tocopherol or probucol contributing to the reduction of airway inflammation.
These findings indicate that alpha-tocopherol and probucol suppress allergic responses in asthma model mice, although these two drugs cause suppression in different ways that are unrelated to antioxidation.
我们使用经卵清蛋白致敏和激发的幼年哮喘模型小鼠，研究抗氧化剂在气道对乙酰胆碱高反应性中的作用。
在首次致敏前14天，将小鼠分别喂食正常饮食、补充α-生育酚的饮食或补充普罗布考的饮食。它们每隔12天用抗原进行免疫，从第二次免疫后10天开始，每隔4天使用超声雾化器让它们接触抗原3次。在最后一次吸入抗原24小时后，测量气道对乙酰胆碱的反应性并收集支气管肺泡灌洗液（BALF）。还进行了血液和肺组织研究。
在最后一次抗原激发24小时后，补充α-生育酚小鼠的BALF中IL-4和IL-5均显著降低。补充普罗布考小鼠的IL-5水平也降低，但IL-4水平无差异。补充普罗布考小鼠的血清IgE水平降低。灌洗液的细胞分类率显示，由于补充抗氧化剂，嗜酸性粒细胞显著减少。补充抗氧化剂的小鼠对乙酰胆碱的气道高反应性也受到抑制。在肺组织的组织学切片中，补充抗氧化剂的小鼠炎症细胞和黏液分泌明显减少。我们通过检测BALF和肺组织中的8-异前列腺素以及BALF中的丙烯醛来研究抗氧化剂对我们模型小鼠的影响；然而，我们的实验没有提供证据表明α-生育酚或普罗布考的抗氧化特性有助于减轻气道炎症。
这些发现表明，α-生育酚和普罗布考可抑制哮喘模型小鼠的过敏反应，尽管这两种药物以与抗氧化作用无关的不同方式产生抑制作用。
