Resveratrol suppresses persistent airway inflammation and hyperresponsivess might partially via nerve growth factor in respiratory syncytial virus-infected mice.
Resveratrol suppresses persistent airway inflammation and hyperresponsivess might partially via nerve growth factor in respiratory syncytial virus-infected mice.
复制标题
DOI：
10.1016/j.intimp.2015.05.031
复制
发表时间：
2015-09
影响因子：
5.6
通讯作者：
N. Zang;Simin Li;Wei Li;Xiao-hong Xie;L. Ren;X. Long;Jun Xie;Yu Deng;Z. Fu;Fadi Xu
中科院分区：
文献类型：
--
作者：
N. Zang;Simin Li;Wei Li;Xiao-hong Xie;L. Ren;X. Long;Jun Xie;Yu Deng;Z. Fu;Fadi Xu
呼吸道合胞病毒（RSV）感染与持续性和反复性喘息有关。对于早期毛细支气管炎后持续喘息的后遗症，尚无有效、安全的药物。在这项研究中，我们研究了白藜芦醇对 RSV 感染引起的持续性气道炎症和气道高反应性 (AHR) 的影响。在感染后的连续时间点处死感染 RSV 的小鼠以收集样本并测量炎症细胞的数量以及干扰素-γ (IFN-γ)、神经生长因子 (NGF) 和脑源性神经营养因子 (BDNF) 的水平。白藜芦醇给药后检测气道炎症、AHR、NGF、BDNF水平。此外，Ab-NGF 用于研究 NGF 在 RSV 诱导的长期气道炎症和 AHR 中的作用。我们发现，在第 60 天，RSV 感染小鼠的肺部仍可检测到 RSV RNA，并伴随着持续 60 天的持续气道炎症和 AHR。 BALF中的IFN-γ水平在RSV感染后第7天增加，但到第14天降至正常水平，而NGF和BDNF水平从第14天到第60天逐渐增加。此外，白藜芦醇治疗后，BALF中的细胞总数减少；浸润肺部的炎症细胞数量也较少。白藜芦醇减弱气道对乙酰甲胆碱的反应，并显着降低 BALF 中的 NGF 水平，而不影响 BDNF 水平。此外，Ab-NGF 给药后，与 RSV 持续存在相关的气道炎症和 AHR 有所减弱。总之，白藜芦醇抑制持续性气道炎症，AHR 可能部分通过降低 RSV 感染后 NGF 的水平来抑制。
Respiratory syncytial virus (RSV) infection is involved in persistent and recurrent wheezing. There are no effective and safe drugs for the sequelae of persistent wheezing after early bronchiolitis. In this study, we investigated the effect of resveratrol on persistent airway inflammation and airway hyperresponsiveness (AHR) induced by RSV infection. RSV-infected mice were sacrificed at serial time points after infection to collect samples and measure the number of inflammatory cells and levels of interferon-gamma (IFN-γ), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF). Airway inflammation, AHR, and the levels of NGF and BDNF were detected after resveratrol administration. Furthermore, Ab-NGF was used to investigate the role of NGF in RSV-induced prolonged airway inflammation and AHR. We found that RSV RNA remained detectable in the lungs of RSV-infected mice on day 60, accompanying persistent airway inflammation and AHR for 60 days. IFN-γ levels in BALF were increased on day 7 but reduced to normal levels by day 14 post-RSV infection, while NGF and BDNF levels gradually increased from day 14 to 60. Furthermore, after resveratrol treatment, the total number of cells in BALF was reduced; the number of inflammatory cells infiltrating the lungs was also lower. Resveratrol attenuated the airway response to methacholine and significantly decreased NGF levels in BALF without affecting BDNF levels. Moreover, airway inflammation and AHR associated with RSV persistence were attenuated after Ab-NGF administration. In all, resveratrol suppresses persistent airway inflammation and AHR might partially through reducing the levels of NGF after RSV infection.