抗哮喘简化草药干预对豚草致敏性哮喘小鼠模型中性粒细胞占优势的气道炎症的影响。
Effect of Antiasthma Simplified Herbal Medicine Intervention on neutrophil predominant airway inflammation in a ragweed sensitized murine asthma model.
机构信息
Division of Allergy and Immunology, Department of Pediatrics, The Icahn School of Medicine at Mount Sinai, New York, New York.
Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, The Icahn School of Medicine at Mount Sinai, New York, New York.
出版信息
Ann Allergy Asthma Immunol. 2014 Apr;112(4):339-47.e1-2. doi: 10.1016/j.anai.2014.01.021.
BACKGROUND
Neutrophil-predominant asthma is less responsive to steroids and associated with poorer disease control. The effects of Antiasthma Simplified Herbal Medicine Intervention (ASHMI), a traditional Chinese medicine formula reported to be efficacious in asthmatic patients and murine asthma models, on neutrophil predominant asthma are unknown.
OBJECTIVE
To determine the effects of standard ASHMI and refined formula ASHMI (ASHMI(II)) in a neutrophil-predominant murine model of ragweed (RW) asthma and explore underlying mechanisms.
METHODS
BALB/c mice were systemically sensitized, intranasally challenged with RW extract, and orally treated with ASHMI, ASHMI(II), or vehicle (water). In a separate experiment, some RW sensitized mice were treated with dexamethasone before challenge. After RW challenge, airway hyperreactivity (AHR), total and differential bronchoalveolar lavage fluid leukocyte counts, lung histologic features, and bronchoalveolar lavage fluid cytokine and chemokine levels were assessed. RW stimulation of the murine macrophage cell line RAW264.7 was used to determine effects of ASHMI active compound ganoderic acid C1 (GAC1) on tumor necrosis factor α (TNF-α) production and regulation of phosphorylated IκB and histone deacetylase 2 (HDAC2) levels.
RESULTS
ASHMI and ASHMI(II) markedly reduced AHR, mucous production, neutrophilic inflammation, and TNF-α, interleukin 8, and interleukin 17 levels and decreased eosinophilic inflammation and TH2 responses in vivo (P < .01-.001 for all). GAC1 inhibited TNF-α production in RW-stimulated RAW264.7 cells in association with suppression of phosphorylated IκB and increased HDAC2 expression. Dexamethasone failed to reduce AHR and neutrophilic inflammation.
CONCLUSION
ASHMI treatment was efficacious in a murine model of neutrophil-predominant asthma via modulation of innate chemokines, TH2 responses, nuclear factor-κB, and HDAC2. ASHMI, and/or its constituent GAC1, may be a valuable option for treating neutrophil-predominant asthma.
背景
嗜中性粒细胞占优势的哮喘对类固醇反应不佳，且与疾病控制较差相关。Antiasthma Simplified Herbal Medicine Intervention (ASHMI)，一种传统中药配方，据报道对哮喘患者和小鼠哮喘模型有效，但其对嗜中性粒细胞占优势的哮喘的影响尚不清楚。
目的
确定标准 ASHMI 和精制配方 ASHMI (ASHMI(II)) 在豚草 (RW) 哮喘嗜中性粒细胞占优势的小鼠模型中的作用，并探讨潜在机制。
方法
BALB/c 小鼠全身致敏，用 RW 提取物鼻内激发，并用 ASHMI、ASHMI(II)或载体（水）口服治疗。在另一个实验中，一些 RW 致敏的小鼠在用 RW 激发前用地塞米松治疗。RW 激发后，评估气道高反应性 (AHR)、总和差异支气管肺泡灌洗液白细胞计数、肺组织学特征以及支气管肺泡灌洗液细胞因子和趋化因子水平。使用 RW 刺激小鼠巨噬细胞系 RAW264.7 来确定 ASHMI 活性化合物灵芝酸 C1 (GAC1) 对肿瘤坏死因子-α (TNF-α) 产生的影响，以及对磷酸化 IκB 和组蛋白去乙酰化酶 2 (HDAC2) 水平的调节作用。
结果
ASHMI 和 ASHMI(II) 显著降低 AHR、黏液产生、嗜中性粒细胞炎症和 TNF-α、白细胞介素 8 和白细胞介素 17 水平，并降低嗜酸性粒细胞炎症和 TH2 反应（所有 P <.01-.001）。GAC1 抑制 RW 刺激的 RAW264.7 细胞中 TNF-α 的产生，同时抑制磷酸化 IκB 和增加 HDAC2 表达。地塞米松未能降低 AHR 和嗜中性粒细胞炎症。
结论
ASHMI 治疗在嗜中性粒细胞占优势的哮喘小鼠模型中是有效的，通过调节先天趋化因子、TH2 反应、核因子-κB 和 HDAC2。ASHMI 和/或其组成 GAC1 可能是治疗嗜中性粒细胞占优势的哮喘的一种有价值的选择。
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