Inhibition of airway inflammation, hyperresponsiveness and remodeling by soy isoflavone in a murine model of allergic asthma
Inhibition of airway inflammation, hyperresponsiveness and remodeling by soy isoflavone in a murine model of allergic asthma
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DOI：
10.1016/j.intimp.2011.02.001
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发表时间：
2011-08-01
影响因子：
5.6
通讯作者：
Xie, Qiang-Min
中科院分区：
文献类型：
--
作者：
Bao, Zhao-Seng;Hong, Ling;Xie, Qiang-Min
流行病学研究表明，大豆异黄酮的饮食摄入量增加与咳嗽和过敏性呼吸道症状的自我报告减少有关，但大豆异黄酮对哮喘模型的药效学作用尚未得到很好的描述。在此，我们假设大豆黄酮可能对哮喘小鼠的气道高反应性、炎症和气道重塑具有潜在的影响。致敏小鼠和卵白蛋白激发气道炎症。评估支气管肺泡灌洗液的炎性细胞计数和细胞因子水平。检查肺组织的细胞浸润、粘液高分泌和气道重塑，以及炎症生物标志物的表达。采用直接气道阻力分析法监测气道高反应性。口服大豆异黄酮可显著降低卵白蛋白诱导的气道对静脉注射乙酰甲胆碱的高反应性，并抑制卵白蛋白诱导的嗜酸性粒细胞计数增加。全肺裂解物的RT-PCR分析显示，大豆黄酮显著抑制卵清蛋白诱导的嗜酸性粒细胞趋化因子，白细胞介素（IL）-5，IL-4和基质金属蛋白酶-9的mRNA表达，并以剂量依赖性方式增加干扰素（IFN）-γ和金属蛋白酶组织抑制剂-1的mRNA表达。大豆黄酮还基本上恢复了支气管肺泡灌洗液中的IFN-γ/IL-4（Th 1/Th 2）水平。此外，组织学研究显示大豆黄酮显著抑制卵清蛋白诱导的肺组织嗜酸性粒细胞浸润、气道粘液产生和肺组织胶原沉积。我们的研究结果表明，大豆蛋白作为营养补充剂可能为治疗气道炎症性疾病提供一种新的手段。(C)2011 Elsevier B. V.保留所有权利。
Epidemiologic studies have associated higher dietary consumption of soy isoflavones with decreased self-report of cough and allergic respiratory symptoms, but the pharmacodynamic effects of soy isoflavone on asthmatic model have not been well-described. Here, we hypothesized that soy isoflavone may have potential effects on airway hyperresponsiveness, inflammation and airway remodeling in a murine of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts, and for cytokine levels. Lung tissues were examined for cell infiltration, mucus hypersecretion and airway remodeling, and for the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Oral administration of soy isoflavone significantly reduced ovalbumin-induced airway hyperresponsiveness to intravenous methacholine, and inhibited ovalbumin-induced increases in eosinophil counts. RT-PCR analysis of whole lung lysates revealed that soy isoflavone markedly suppressed ovalbumin-induced mRNA expression of eotaxin, interleukin(IL)-5, IL-4 and matrix metalloproteinase-9, and increased mRNA expression of interferon (IFN)-gamma and tissue inhibitor of metalloproteinase-1 in a dose-dependent manner. Soy isoflavone also substantially recovered IFN-gamma/IL-4 (Th1/Th2) levels in bronchoalveolar lavage fluid. In addition, histologic studies showed that soy isoflavone dramatically inhibited ovalbumin-induced lung tissue eosinophil infiltration, airway mucus production and collagen deposition in lung tissues. Our findings suggest that soy isoflavone as nutritional supplement may provide a novel means for the treatment of airway inflammatory disease. (C) 2011 Elsevier B.V. All rights reserved.