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槲皮素治疗对变应性气道炎症小鼠模型上皮来源细胞因子及上皮细胞凋亡的影响

Effects of Quercetin Treatment on Epithelium-derived Cytokines and Epithelial Cell Apoptosis in Allergic Airway Inflammation Mice Model.

作者信息

Caglayan Sozmen Sule, Karaman Meral, Cilaker Micili Serap, Isik Sakine, Bagriyanik Alper, Arikan Ayyildiz Zeynep, Uzuner Nevin, Anal Ozden, Karaman Ozkan

机构信息

Department of Pediatrics, Division of Pediatric Allergy and Immunology, Faculty of Medicine,  Dokuz Eylul University, Izmir,Turkey.

Department of Medical Microbiology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.

出版信息

Iran J Allergy Asthma Immunol. 2016 Dec;15(6):487-497.

PMID:28129681
Abstract

Quercetin is a dietary flavonoid which has anti-inflammatory effects. This study aimed to evaluate the influence of quercetin on histopathological aspects and airway epithelium in  allergic airway  inflammation mice model. Twenty-eight BALB/c mice were randomly divided into four groups: Group I (control), Group II (untreated mice with allergic airway inflammation), Group III (allergic airway inflammation quercetin-treated [16mg/kg/day]), Group IV (allergic airway inflammation dexamethasone-treated [1mg/kg/day]). Ovalbumin was administered intraperitoneally and via inhalation to achieve allergic airway inflammation mice model and treatments were also given intraperitoneally. Epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness were examined on samples isolated from lung. Immunohistochemical evaluationof lung tissues was performed using  IL-25, IL-33, thymic stromal lymphopoietin (TSLP), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases(caspase)-3 antibodies. IL-4, IL-25, IL-33, TSLP were quantified in bronchoalveolar lavage (BAL) and OVAspecific IgE levels was measured in serum by standard ELISA protocols. IL-25, IL-33, thymic stromal lymphopoietin (TSLP) and cysteine-dependent aspartate-specific proteases (caspase)-3. Quercetin treatment led to lower epithelial thickness, subepithelial smooth muscle thickness, goblet and mast cell numbers compared to untreated  mice with allergic airway inflammation (p<0.05). However, quercetin treatment was not effective on improving basal membane thickness. Immunohistochemical scores of IL-25, IL-33, TSLP, caspase-3 and TUNEL were lower in quercetin-treated mice  t compared to untreated mice with allergic airway inflammation (p<0.05). IL-4, IL-25, IL-33, TSLP levels in BAL and OVA-specific IgE in serum were lower in quercetin treated mice compared to untreated mice (p<0.05). These findings suggest that quercetin improves chronic histopathological changes except basal membrane thickness in lung tissue and its beneficial effects on inflammation might be related to modulating epithelium derived cytokines and epithelial apoptosis.

摘要

槲皮素是一种具有抗炎作用的膳食类黄酮。本研究旨在评估槲皮素对变应性气道炎症小鼠模型的组织病理学特征及气道上皮的影响。将28只BALB/c小鼠随机分为四组:第一组(对照组)、第二组(变应性气道炎症未治疗小鼠)、第三组(变应性气道炎症槲皮素治疗组[16mg/kg/天])、第四组(变应性气道炎症地塞米松治疗组[1mg/kg/天])。通过腹腔注射和吸入给予卵清蛋白以建立变应性气道炎症小鼠模型,治疗也通过腹腔注射给予。对从肺中分离的样本检查上皮厚度、上皮下平滑肌厚度、肥大细胞和杯状细胞数量以及基底膜厚度。使用白细胞介素-25(IL-25)、白细胞介素-33(IL-33)、胸腺基质淋巴细胞生成素(TSLP)、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)和半胱氨酸天冬氨酸特异性蛋白酶(caspase)-3抗体对肺组织进行免疫组织化学评估。通过支气管肺泡灌洗(BAL)对IL-4、IL-25、IL-33、TSLP进行定量,并通过标准酶联免疫吸附测定(ELISA)方法测量血清中的卵清蛋白特异性IgE水平。IL-25、IL-33、胸腺基质淋巴细胞生成素(TSLP)和半胱氨酸天冬氨酸特异性蛋白酶(caspase)-3。与变应性气道炎症未治疗小鼠相比,槲皮素治疗导致上皮厚度、上皮下平滑肌厚度、杯状细胞和肥大细胞数量降低(p<0.05)。然而,槲皮素治疗对改善基底膜厚度无效。与变应性气道炎症未治疗小鼠相比,槲皮素治疗小鼠中IL-25、IL-33、TSLP、caspase-3和TUNEL的免疫组织化学评分较低(p<0.05)。与未治疗小鼠相比,槲皮素治疗小鼠的BAL中的IL-4、IL-25、IL-33、TSLP水平以及血清中的卵清蛋白特异性IgE较低(p<0.05)。这些发现表明,槲皮素可改善肺组织中除基底膜厚度外的慢性组织病理学变化,其对炎症的有益作用可能与调节上皮来源的细胞因子和上皮细胞凋亡有关。

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