原花青素抑制哮喘小鼠气道炎症及气道高反应性
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江苏省重点医学开放课题(KF200920),常州市重点医学创新人才基金,常州市卫生局重大课题(ZD201002),常州市卫生局青年基金(QN200904)资助


Effect of grape seed proanthocyanidin extract on airway inflammation and hyperresponsiveness in a murine model of asthma
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    摘要:

    目的:探讨葡萄籽提取物原花青素对急性哮喘模型小鼠气道炎症和气道高反应的作用及其机制-方法:选择32只8周龄SPF级BALB/c雌性小鼠,随机平均分成4组:对照组-哮喘组-布地奈德组和原花青素组-卵白蛋白(OVA)致敏和激发制作哮喘模型-小鼠末次激发24 h后,检测小鼠气道阻力;苏木精-伊红(HE)染色观察气道炎性细胞浸润;过碘酸雪夫(PAS)染色观察杯状细胞增生-气道黏液分泌;酶联免疫吸附法(ELISA)检测血清总IgE和支气管肺泡灌洗液(BALF)中白细胞介素(IL)-4和干扰素(INF)-γ;免疫印迹(Western blot)测定肺组织中诱导型一氧化氮合酶(iNOS)表达水平-结果:与正常组相比,哮喘组气道阻力-气道炎症-BALF中细胞计数和嗜酸性粒细胞分类计数-IL-4-血清总IgE以及肺内iNOS蛋白表达明显增高(P < 0.01),而BALF中INF-γ明显降低(P < 0.01);与哮喘组相比,除INF-γ升高外,原花青素治疗组和布地奈德组各项指标均降低(P < 0.05)-结论:原花青素通过减少肺内iNOS的表达而减轻哮喘小鼠气道炎症和气道高反应性,具有潜在的临床应用前景-

    Abstract:

    Objective:To explore the effect and mechanism of grape seed proanthocyanidin extract(GSPE) on airway inflammation and hyperresponsiveness in a murine model of allergic asthma. Methods:BALB/c mice(n=32; aged 8 weeks) were randomly and averagely divided into 4 groups: control group, asthma group, budesonide group and GSPE group. The mice were sensitized and challenged with ovalbumin(OVA) to produce a murine model of asthma. The GSEP group mice were intraperitoneally injected with GSPE[50 mg/(kg·d)]. Mice in the budesonide group were treated with aerosolized budesonide. The airway responsiveness of mice in each group to acetylcholine chloride (Ach) was evaluated. HE staining and PAS staining were used to observe airway inflammation in lung tissue and airway mucus secretion, respectively. Quantification of cytokines in bronchoalveolar lavage fluid(BALF) and total serum immunoglobulin E(IgE) were detected by ELISA. The protein expression of inducible nitric oxide synthase(iNOS) in lung tissue was evaluated by Western blot analysis. Results:As compared with the control group, the asthma group showed significant increase of airway resistance, total inflammatory cell and eosinophil counts and interleukin(IL)-4 level in BALF, total IgE level in serum, as well as iNOS expression, while the level of interferon (IFN)-γ in BALF decreased (P < 0.05). Remarkable reduction was observed in all the above items except IFN-γ level, which increased, in the GSEP group and the budesonide group(P < 0.05). Conclusion:GSPE decreases the progression of airway inflammation and hyperresponsiveness by downregulating the iNOS expression, promising to be a potential drug in the treatment of allergic asthma.

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周丹阳,曹 琦,黄 茂,张 倩,韦国桢.原花青素抑制哮喘小鼠气道炎症及气道高反应性[J].南京医科大学学报(自然科学版),2011,(7):981-985

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  • 收稿日期:2011-01-21
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