Fangxiao Formula alleviates airway inflammation and remodeling in rats with asthma via suppression of transforming growth factor-β/Smad3 signaling pathway
Fangxiao Formula alleviates airway inflammation and remodeling in rats with asthma via suppression of transforming growth factor-β/Smad3 signaling pathway
复制标题
防消方通过抑制转化生长因子-β/Smad3信号通路减轻哮喘大鼠气道炎症和重塑
DOI：
10.1016/j.biopha.2019.109429
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发表时间：
2019-11-01
影响因子：
7.5
通讯作者：
Chen, Jian
中科院分区：
文献类型：
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作者：
Ge, Yuqing;Cheng, Rubin;Chen, Jian
哮喘是一种常见的阻塞性气道疾病，其特征是炎症和重塑，肺功能进行性下降。防哮方是一种对哮喘患者有显著临床疗效的中药，但其作用机制尚不清楚。本研究旨在观察FXF对哮喘大鼠气道炎症和重塑的抑制作用，并探讨其对TGF-β/Smads信号通路的影响。卵清蛋白致敏6周建立大鼠哮喘模型。OVA攻击的动物随机分为5组，并接受不同浓度的FXF或地塞米松。空白对照组仅给予生理盐水。取肺组织行HE染色、PAS染色、气道壁厚度及胶原沉积测定。ELISA法检测支气管肺泡灌洗液（BAL）中炎性细胞因子的产生。免疫组化法检测FXF治疗后肺组织中α-SMA和PCNA的表达。通过免疫组织学和蛋白质印迹法评估TGF-β的水平，并通过蛋白质印迹法分析确定p-Smad 2/3蛋白的表达。结果表明，FXF可减轻哮喘大鼠模型的炎症细胞浸润，减少Th 2细胞因子的产生，同时增加Th 1细胞因子的水平。此外，FXF减少过敏原诱导的气道壁厚度增加、杯状细胞增生和胶原沉积。FXF治疗后TGF-β和p-Smad 3的表达水平明显降低。这些结果表明，FXF通过恢复Th 1/Th 2细胞因子和TGF-β/Smad-3通路的平衡来减轻气道炎症和重塑，从而为哮喘患者提供了潜在的治疗方法。
Asthma is a common obstructive airway disease characterized by inflammation and remodeling with a progressive decline in lung function. Fangxiao Formula (FXF) is an herbal medicine that has achieved significant clinical benefits toward asthma patients, but the relevant mechanism has not yet been clarified. The aim of this study was to determine the inhibitory effects of FXF on airway inflammation and remodeling, and investigate the activities of TGF-beta/Smads signaling pathway in the rat asthma model. Rats were sensitized by ovalbumin (OVA) for six weeks to establish the asthma experimental model. OVA-challenged animals were randomly divided into 5 groups and received different concentrations of FXF or dexamethasone. The animals in blank control group received saline only. Lung tissues were collected and analyzed for determining the inflammatory cells infiltration, HE and PAS staining, airway wall thickness and collagen deposition. The productions of inflammatory cytokine productions were analyzed by ELISA in the bronchoalveolar lavage (BAL) fluid. Immunohistochemical analysis was performed to measure the expression of alpha-SMA and PCNA in lung tissue after the treatment of FXF. The levels of TGF-beta were assessed by both immunohistology and western blotting, and the expression of p-Smad2/3 proteins were determined by western blotting analysis. Our results indicated that FXF attenuated the infiltration of inflammatory cells, decreased the production of Th2 cytokines and simultaneously increased the levels of Th1 cytokine in the asthma rat model. In addition, FXF reduced allergen-induced increased airway wall thickness, goblet cell hyperplasia and collagen deposition. Furthermore, the expression levels of TGF-beta and p-Smad3 were obviously reduced after the treatment of FXF. These results indicate that FXF alleviates airway inflammation and remodeling by restoring the balance of Th1/Th2 cytokines and the TGF-beta/Smad-3 pathway, therefor providing potential therapeutic approach for asthmatic patients.