N-乙酰半胱氨酸及其在过敏性哮喘动物模型中的治疗潜力

IF 2 4区 医学 Q3 RESPIRATORY SYSTEM
Lukáš Smieško, Jozef Mažerik, Eduard Gondáš, Matúš Dohál, Marta Jošková, Martina Šutovská, Soňa Fraňová
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引用次数: 0

摘要

背景:n -乙酰半胱氨酸(NAC)是一种经典的解黏液剂,除具有解黏液活性外,还具有抗氧化活性。这可能有助于治疗慢性炎症性气道疾病,包括哮喘。背景:我们在实验性豚鼠变应性炎症模型中评估了NAC在给药10天后(20和60 mg/(kg·d))调节气道防御机制、气道反应性、炎症和重塑的能力。方法:采用多重检测法测定支气管肺泡灌洗液中炎症因子(白细胞介素:IL-4、IL-5、IL-10、IL-12、IL-13)、粒细胞巨噬集落刺激因子(GM-CSF)、干扰素-γ (IFN-γ)、肿瘤坏死因子-α (TNF-α)的浓度。采用酶联免疫吸附法测定肺匀浆中重塑标志物转化生长因子β -1 (TGF-β1)的浓度。在体内,测定了特定气道阻力和咳嗽次数的变化。体外评价气管平滑肌反应性。纤毛搏动频率(CBF)提示纤毛粘液清除。结果:高剂量NAC给药10天可导致调节细胞因子IL-4、IL-5和GM-CSF显著降低。NAC在两种给药方案下均降低TGF-β1水平。高剂量NAC可减少化学诱导的咳嗽反射次数和CBF。NAC对气道高反应性参数无影响。结论:NAC是一种多因子药物,在我们的变应性炎症实验条件下,NAC对调节性细胞因子和生长因子水平有正向影响,可能导致气道防御机制强度降低。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
N-Acetylcysteine and Its Therapeutic Potential in an Animal Model of Allergic Asthma.

Background: N-acetylcysteine (NAC) is a classical mucolytic agent that, in addition to its mucolytic activity, also exhibits antioxidant activity. This could be beneficial in treating chronic inflammatory airway diseases, including asthma. Background: We evaluated the ability of NAC to modulate airway defense mechanisms, airway reactivity, inflammation, and remodeling after 10 days of administration [20 and 60 mg/(kg·d)] in an experimental guinea pig model of allergic inflammation. Methods: The concentrations of inflammatory cytokines (interleukins: IL-4, IL-5, IL-10, IL-12, and IL-13), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) were measured in bronchoalveolar lavage fluid using a multiplex detection method. The concentration of remodeling marker transforming growth factor beta-1 (TGF-β1) was measured in lung homogenates using enzyme-linked immunosorbent assay. In vivo, changes in specific airway resistance and number of cough efforts were determined. Tracheal smooth muscle reactivity was evaluated in vitro. Ciliary beat frequency (CBF) indicated mucociliary clearance. Results: A 10-day administration of NAC at a higher dosage led to a significant decrease in the regulatory cytokines IL-4, IL-5, and GM-CSF. NAC, in both dosing schedules, decreased the levels of TGF-β1. NAC at a higher dosage reduced the number of chemically induced cough reflexes and CBF. NAC did not affect airway hyperreactivity parameters. Conclusion: NAC is a multifactorial drug, and under our experimental conditions of allergic inflammation, it showed positive effects on the levels of regulatory cytokines and growth factors, which probably led to a reduction in the intensity of airway defense mechanisms.

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来源期刊
CiteScore
6.70
自引率
2.90%
发文量
34
审稿时长
>12 weeks
期刊介绍: Journal of Aerosol Medicine and Pulmonary Drug Delivery is the only peer-reviewed journal delivering innovative, authoritative coverage of the health effects of inhaled aerosols and delivery of drugs through the pulmonary system. The Journal is a forum for leading experts, addressing novel topics such as aerosolized chemotherapy, aerosolized vaccines, methods to determine toxicities, and delivery of aerosolized drugs in the intubated patient. Journal of Aerosol Medicine and Pulmonary Drug Delivery coverage includes: Pulmonary drug delivery Airway reactivity and asthma treatment Inhalation of particles and gases in the respiratory tract Toxic effects of inhaled agents Aerosols as tools for studying basic physiologic phenomena.
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