Wang Xu, Liu Chun, Wu Liucheng, Zhu Shunxing
Laboratory Animals Center, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
Laboratory Animals Center, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
Eur J Pharmacol. 2016 Oct 5;788:343-350. doi: 10.1016/j.ejphar.2016.07.040. Epub 2016 Aug 4.
Recent studies have implicated that Hypoxia-inducible factor 1α (HIF-1α) plays an integral role in the pathogenesis of allergic rhinitis and asthma. In the present study, we showed that HIF-1α antagonist YC-1, 3-(5-hydroxymethyl-2-furyl)-1-benzylindazole, elicited a potent allergy-ameliorating effect in a rat model of ovalbumin (OVA)-sensitized combined allergic rhinitis and asthma syndrome (CARAS). We revealed that YC-1 administration markedly impaired the total number and percentage of eosinophil in bronchoalveolar lavage fluid (BAL Fluid) of the rats, suggesting that YC-1 might attenuate lung and nasal mucosal inflammation in OVA-sensitized rats. Moreover, histological examination found that OVA-induced pathological alterations were evidently attenuated following YC-1 administration. In addition, immunohistochemistrial analysis indicated that YC-1 treatment decreased the expression of HIF-1α in rat lungs and nasal mucosa. Notably, Nuclear factor kappa B (NF-κB) p65 and Peroxisome proliferator-activated receptor α (PPARα), two important regulators of inflammatory responses, were also significantly down-regulated following YC-1 administration. Real-time PCR analysis confirmed that YC-1 impaired the expression of HIF-1α, NF-κB and PPARα in CARAS model. These findings together indicated that YC-1 exerted remarkable anti-allergic effects through the modulation of inflammatory pathways, implying that YC-1 may potentially serve as a novel anti-CARAS medicine in clinical patients.
最近的研究表明，缺氧诱导因子1α（HIF-1α）在过敏性鼻炎和哮喘的发病机制中起着不可或缺的作用。在本研究中，我们发现HIF-1α拮抗剂YC-1，即3-(5-羟甲基-2-呋喃基)-1-苄基吲唑，在卵清蛋白（OVA）致敏的合并过敏性鼻炎和哮喘综合征（CARAS）大鼠模型中具有显著的抗过敏作用。我们发现，给予YC-1可显著减少大鼠支气管肺泡灌洗液（BAL液）中嗜酸性粒细胞的总数和百分比，这表明YC-1可能减轻OVA致敏大鼠的肺部和鼻黏膜炎症。此外，组织学检查发现，给予YC-1后，OVA诱导的病理改变明显减轻。另外，免疫组织化学分析表明，YC-1处理可降低大鼠肺和鼻黏膜中HIF-1α的表达。值得注意的是，炎症反应的两个重要调节因子核因子κB（NF-κB）p65和过氧化物酶体增殖物激活受体α（PPARα）在给予YC-1后也显著下调。实时PCR分析证实，YC-1可抑制CARAS模型中HIF-1α、NF-κB和PPARα的表达。这些发现共同表明，YC-1通过调节炎症途径发挥显著的抗过敏作用，这意味着YC-1可能有潜力成为临床患者治疗CARAS的新型药物。
