Hyperoxia exposure of immature lungs contributes to lung injury and airway hyperreactivity. Up to now, treatments of airway hyperreactivity induced by hyperoxia exposure have been ineffective. The aim of this study was to investigate the effects of quercetin on hyperoxia-induced airway hyperreactivity, impaired relaxation, and lung inflammation. Newborn rats were exposed to hyperoxia (FiO2 > 95%) or ambient air (AA) for seven days. Subgroups were injected with quercetin (10 mg·kg-1·day-1). After exposures, tracheal cylinders were prepared for in vitro wire myography. Contraction to methacholine was measured in the presence or absence of organ bath quercetin and/or Nω-nitro-L-arginine methyl ester (L-NAME). Relaxation responses were evoked in preconstricted tissues using electrical field stimulation (EFS). Lung tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) levels were measured by enzyme-linked immunosorbent assay (ELISA). A P < 0.05 was considered statistically significant. Contractile responses of tracheal smooth muscle (TSM) of hyperoxic animals were significantly increased compared with AA animals (P < 0.001). Treatment with quercetin significantly reduced contraction in hyperoxic groups compared with hyperoxic control (P < 0.01), but did not have any effect in AA groups. In hyperoxic animals, relaxation of TSM was significantly reduced compared with AA animals (P < 0.001), while supplementation of quercetin restored the lost relaxation in hyperoxic groups. Incubation of preparations in L-NAME significantly reduced the quercetin effects on both contraction and relaxation (P < 0.01). Treatment of hyperoxic animals with quercetin significantly decreased the expression of TNF-α and IL-1β compared with hyperoxic controls (P < 0.001 and P < 0.01, respectively).The findings of this study demonstrate the protective effect of quercetin on airway hyperreactivity and suggest that quercetin might serve as a novel therapy to prevent and treat neonatal hyperoxia-induced airway hyperreactivity and inflammation.

中文翻译：

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槲皮素补充剂可减轻暴露于高氧的幼鼠的气道高反应性并恢复气道松弛。

未成熟肺部的高氧暴露会导致肺损伤和气道高反应性。到目前为止，对高氧暴露引起的气道高反应性的治疗还没有效果。本研究的目的是研究槲皮素对高氧诱导的气道高反应性、松弛受损和肺部炎症的影响。新生大鼠暴露于高氧 (FiO2 > 95%) 或环境空气 (AA) 中 7 天。各亚组注射槲皮素（10 mg·kg-1·day-1）。暴露后，准备气管圆筒用于体外线肌动描记术。在存在或不存在器官浴槲皮素和/或Nω-硝基-L-精氨酸甲酯（L-NAME）的情况下测量乙酰甲胆碱的收缩。使用电场刺激（EFS）在预收缩组织中诱发松弛反应。通过酶联免疫吸附测定（ELISA）测量肺肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平。AP < 0.05 被认为具有统计显着性。与AA动物相比，高氧动物气管平滑肌（TSM）的收缩反应显着增强（P < 0.001）。与高氧对照组相比，槲皮素治疗显着减少了高氧组的收缩（P < 0.01），但对 AA 组没有任何影响。在高氧动物中，与 AA 动物相比，TSM 的松弛度显着降低（P < 0.001），而补充槲皮素则恢复了高氧组失去的松弛度。在 L-NAME 中孵育制剂可显着降低槲皮素对收缩和舒张的影响 (P < 0.01)。与高氧对照组相比，用槲皮素治疗高氧动物可显着降低 TNF-α 和 IL-1β 的表达（分别为 P < 0.001 和 P < 0.01）。本研究结果证明了槲皮素对气道高反应性的保护作用，并提示槲皮素可能作为一种新疗法来预防和治疗新生儿高氧诱导的气道高反应性和炎症。