Zhou Dan-Yang, Fang Su-Rong, Zou Chun-Fang, Zhang Qian, Gu Wei
Nat Prod Commun. 2015 Feb;10(2):257-62.
Asthma is characterized by airway inflammation and airway remodeling. Our previous study revealed that grape seed proanthocyanidin extract (GSPE) could inhibit asthmatic airway inflammation and airway hyper-responsiveness by down-regulation of inducible nitric oxide synthase in a murine model of acute asthma. The present study aimed to evaluate GSPE's effects on airway inflammation and airway remodeling in a chronic asthmatic model. BALB/c mice were sensitized with ovalbumin (OVA) and then were challenged three times a week for 8 weeks. Airway responsiveness was measured at 24 h after the last OVA challenge. HE staining, PAS staining, and Masson staining were used to observe any airway inflammation in the lung tissue, airway mucus secretion, and subepithelial fibrosis, respectively. The cytokines levels in the lavage fluid (BALF) in addition to the total serum immunoglobulin E (IgE) levels were detected by ELISA. Furthermore, lung collagen contents, α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) expression in the airway were assessed by hydroxyproline assay, immunohistochemistry, and Western blot analysis, respectively. GSPE administration significantly suppressed airway resistance as well as reduced the amount of inflammatory cells, especially the eosinophil count, in BALF. Additionally, the GSPE treatment markedly decreased interleukin (IL)-4, IL-13, and vascular endothelial growth factor (VEGF) levels in BALF in addition to the total serum IgE levels. A histological examination demonstrated that GSPE significantly ameliorated allergen-induced lung eosinophilic inflammation and decreased PAS-positive epithelial cells in the airway. The elevated hydroxyproline contents, lung α-SMA contents, and TGF-β1 protein expression that were observed in the OVA mice were also inhibited by GSPE. In conclusion, GSPE could inhibit airway inflammation and airway remodeling in a murine model of chronic asthma, thus providing a potential treatment for asthma.
哮喘的特征是气道炎症和气道重塑。我们之前的研究表明，葡萄籽原花青素提取物（GSPE）在急性哮喘小鼠模型中可通过下调诱导型一氧化氮合酶来抑制哮喘气道炎症和气道高反应性。本研究旨在评估GSPE在慢性哮喘模型中对气道炎症和气道重塑的影响。用卵清蛋白（OVA）对BALB/c小鼠进行致敏，然后每周进行3次激发，持续8周。在最后一次OVA激发后24小时测量气道反应性。分别使用苏木精-伊红（HE）染色、过碘酸雪夫（PAS）染色和Masson染色来观察肺组织中的气道炎症、气道黏液分泌和上皮下纤维化。通过酶联免疫吸附测定（ELISA）检测灌洗液（BALF）中的细胞因子水平以及血清总免疫球蛋白E（IgE）水平。此外，分别通过羟脯氨酸测定、免疫组织化学和蛋白质免疫印迹分析评估气道中的肺胶原含量、α-平滑肌肌动蛋白（α-SMA）和转化生长因子-β1（TGF-β1）表达。给予GSPE可显著抑制气道阻力，并减少BALF中炎症细胞的数量，尤其是嗜酸性粒细胞计数。此外，GSPE治疗还显著降低了BALF中白细胞介素（IL）-4、IL-13和血管内皮生长因子（VEGF）水平以及血清总IgE水平。组织学检查表明，GSPE可显著改善变应原诱导的肺部嗜酸性炎症，并减少气道中PAS阳性上皮细胞。OVA小鼠中观察到的升高的羟脯氨酸含量、肺α-SMA含量和TGF-β1蛋白表达也受到GSPE的抑制。总之，GSPE可抑制慢性哮喘小鼠模型中的气道炎症和气道重塑，从而为哮喘提供一种潜在的治疗方法。
