关键词: Hyperresponsiveness Nrf2/HO-1 signaling dexamethasone histopathological inflammation oxidative stress

Mesh : Animals Asthma / chemically induced drug therapy metabolism Cytokines / metabolism Dexamethasone / therapeutic use Disease Models, Animal Eosine Yellowish-(YS) / therapeutic use Glutathione Peroxidase Hematoxylin / therapeutic use Interleukin-13 Interleukin-4 Interleukin-5 Luteolin / therapeutic use Malondialdehyde Mice Mice, Inbred BALB C Mice, Inbred C57BL NF-E2-Related Factor 2 / metabolism NF-KappaB Inhibitor alpha NF-kappa B / metabolism Ovalbumin / adverse effects Reactive Oxygen Species Superoxide Dismutase

来  源:   DOI:10.1177/15353702221094505

Abstract:
Allergic asthma which is induced by ovalbumin (OVA) is a chronic airway inflammation disease. Isoorientin (Iso) is a natural C-glucosyl flavone with many biological properties. We aimed to evaluate the effectiveness of Iso on OVA-induced allergic asthma. A total of 30 C57BL/6 mice were randomly divided into five groups: control group, OVA group, Dex (dexamethasone, 10 mg/kg) group, low-dose Iso group (Iso-L, 25 mg/kg), and high-dose Iso group (Iso-H, 50 mg/kg). The serum and bronchoalveolar lavage fluid (BALF) were collected for biochemical parameters, the lung tissue was collected for hematoxylin-eosin (H&E) staining, immunohistochemistry (IHC), and western blot. The levels of IL-4, IL-5, IL-13, malondialdehyde (MDA), NO, and reactive oxygen species (ROS) in Iso-L and Iso-H groups were significantly lower than that in model group (p < 0.05). Simultaneously, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity were higher than that in model group (p < 0.05). Iso significantly ameliorated airway hyperresponsiveness. Meanwhile, H&E staining revealed that mice treated with Iso resulted in the ameliorated inflammatory cell infiltration and a reduction in interstitial thickening. The nuclear factor erythroid 2-like 2 (Nrf2) and HO-1 protein expression in Iso-L and Iso-H groups were enhanced over that in model group, while p-NF-κB-p65 and p-IκB-α protein expression was decreased (p < 0.05). Our research indicated that Iso alleviated the OVA-induced allergic asthma, and this effect can be explained by the modulation of Nrf2/HO-1 and NF-κB signaling pathway; thus, the results providing a therapeutic rationale for the treatment of Iso on allergic asthma.
摘要:
由卵清蛋白(OVA)引起的过敏性哮喘是一种慢性气道炎症疾病。Isoorientin(Iso)是一种具有许多生物学特性的天然C-葡萄糖基黄酮。我们旨在评估Iso对OVA诱导的过敏性哮喘的有效性。将30只C57BL/6小鼠随机分为5组:对照组,OVA组,Dex(地塞米松,10mg/kg)组,低剂量Iso组(Iso-L,25mg/kg),和高剂量Iso组(Iso-H,50mg/kg)。收集血清和支气管肺泡灌洗液(BALF)生化指标,收集肺组织进行苏木精-伊红(H&E)染色,免疫组织化学(IHC),和westernblot.IL-4、IL-5、IL-13、丙二醛(MDA)水平,NO,Iso-L和Iso-H组活性氧(ROS)明显低于模型组(p<0.05)。同时,超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性均高于模型组(p<0.05)。Iso显着改善了气道高反应性。同时,H&E染色显示,用Iso处理的小鼠导致炎性细胞浸润的改善和间质增厚的减少。Iso-L和Iso-H组的核因子类2样2(Nrf2)和HO-1蛋白表达较模型组增强,而p-NF-κB-p65和p-IκB-α蛋白表达降低(p<0.05)。我们的研究表明,Iso缓解了OVA诱导的过敏性哮喘,这种效应可以通过Nrf2/HO-1和NF-κB信号通路的调节来解释;该结果为Iso治疗过敏性哮喘提供了治疗依据。
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