麻黄碱通过调控TGF-β1/NF-κB信号通路抑制小鼠的气道炎症反应

Ephedrine Inhibits Airway Inflammatory Responses in Mice Through Modulation of the TGF-β1/NF-κB Signaling Pathway

摘要

为了研究麻黄碱通过调控转化生长因子β1/核因子κB (transforming growth factor-β1/nuclear factor-κB, TGF-β1/NF-κB)信号通路对哮喘小鼠气道炎症和气道重塑的影响, 将BALB/c小鼠随机分为空白对照组、哮喘模型组、麻黄碱低剂量组、麻黄碱高剂量组和地塞米松组, 并利用卵清白蛋白(ovalbumin, OVA)联合氢氧化铝腹腔注射法构建小鼠哮喘模型。药物处理14 d后, 通过无创性肺功能检测法测量小鼠气道反应性, 采用苏木精-伊红染色法(hematoxylin-eosin staining, HE staining)观察小鼠肺组织病理情况, 采用瑞氏-吉姆萨染色法分析小鼠支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)中的炎症细胞比例, 利用酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)检测小鼠血清OVA特异性免疫球蛋白E (immunoglobulin E, IgE)的表达水平及BALF中炎症因子的表达水平, 利用免疫印迹法检测小鼠肺组织TGF-β1/NF-κB通路相关蛋白质的表达水平。结果显示, 麻黄碱可以降低哮喘小鼠血清中OVA特异性IgE及BALF中白细胞介素(interleukin, IL)-4、IL-5、IL-6、IL-13、肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α)的表达水平, 并显著抑制肺组织中TGF-β1/ NF-κB通路相关蛋白质的表达, 从而显著抑制由OVA诱导的小鼠气道高反应性, 并改善哮喘小鼠的肺部炎症。

Abstract

To investigate the effects of ephedrine on airway inflammation and airway remodeling through transforming growth factor-β1/nuclear factor-κB (TGF-β1/NF-κB) signaling pathway, mice were randomly di-vided into control group, asthma model group, low-dose ephedrine group, high-dose ephedrine group and dexamethasone group, and the mouse model of asthma was constructed by intraperitoneal injection with combination of ovalbumin (OVA) and aluminum hydroxide. Fourteen days after the drug treatment, the airway reactivity of mice was measured by non-invasive pulmonary function tests. The lung histopathology of mice and the proportion of inflammatory cells in bronchoalveolar lavage fluid (BALF) were measured by hematoxy-lin-eosin (HE) staining and Wright-Giemsa staining, respectively. The expression levels of serum OVA-spe-cific immunoglobulin E (IgE) and inflammatory factors in BALF were detected by enzyme linked immunosor-bent assay (ELISA), and the expression levels of TGF-β1/NF-κB pathway-related proteins in lung tissues were analyzed by immunoblot. The results showed that, in asthmatic mice, ephedrine reduced the OVA-specific IgE antibody levels in sera and interleukin (IL)-4, IL-5, IL-6, IL-13 and tumor necrosis factor-α (TNF-α) levels in BALF, and significantly inhibited the expression of TGF-β1/NF-κB pathway-related proteins in lung tissues. The drug could therefore significantly reduce OVA-induced airway hyperresponsiveness and ameliorate lung inflammation.

关键词

麻黄碱 / 哮喘 / 气道炎症 / 抗炎 / TGF-β1/NF-κB通路

Key words

ephedrine / asthma / airway inflammation / antiinflammation / TGF-β1/NF-κB pathway