4型磷酸二酯酶抑制剂罗氟司特对烟曲霉致敏小鼠早期和晚期过敏反应及气道高反应性的影响。
Effects of the phosphodiesterase type 4 inhibitor roflumilast on early and late allergic response and airway hyperresponsiveness in Aspergillus-fumigatus-sensitized mice.
作者信息
Hoymann Heinz-Gerd, Wollin Lutz, Muller Meike, Korolewitz Regina, Krug Norbert, Braun Armin, Beume Rolf
机构信息
Fraunhofer Institute of Toxicology and Experimental Medicine (Fraunhofer ITEM), Hannover, Germany.
出版信息
Pharmacology. 2009;83(3):188-95. doi: 10.1159/000196814. Epub 2009 Jan 29.
BACKGROUND
Inhibitory effects of roflumilast on responses characteristic of allergic asthma were investigated in a fungal asthma model in BALB/c mice.
METHODS
Mice were sensitized with Aspergillus antigen (Afu) and exposed to Afu or vehicle, and given roflumilast 1 or 5 mg/kg. Early airway response (EAR) and late airway hyperresponsiveness (AHR) to methacholine were measured via plethysmography. Bronchoalveolar lavage (BAL) was used to assess inflammatory cell count.
RESULTS
In Afu-exposed mice, roflumilast dose-dependently reduced the EAR [26% at 1 mg/kg (NS) and 94% at 5 mg/kg (p < 0.01)] and AHR [46% at 1 mg/kg (NS) and 128% at 5 mg/kg (p < 0.05)]. Roflumilast 5 mg/kg reduced neutrophil, eosinophil and lymphocyte counts [87% (p < 0.01), 40% (NS) and 67% (p < 0.01), respectively] in BAL fluid versus controls.
CONCLUSIONS
In this model, roflumilast inhibited the EAR, suppressed AHR and reduced inflammatory cell infiltration.
背景
在BALB/c小鼠的真菌性哮喘模型中研究了罗氟司特对过敏性哮喘反应特征的抑制作用。
方法
用曲霉抗原（Afu）致敏小鼠，使其暴露于Afu或赋形剂，并给予1或5mg/kg的罗氟司特。通过体积描记法测量对乙酰甲胆碱的早期气道反应（EAR）和晚期气道高反应性（AHR）。采用支气管肺泡灌洗（BAL）评估炎症细胞计数。
结果
在暴露于Afu的小鼠中，罗氟司特剂量依赖性地降低了EAR [1mg/kg时降低26%（无统计学意义），5mg/kg时降低94%（p<0.01）]和AHR [1mg/kg时降低46%（无统计学意义），5mg/kg时降低128%（p<0.05）]。与对照组相比，5mg/kg的罗氟司特降低了BAL液中的中性粒细胞、嗜酸性粒细胞和淋巴细胞计数[分别为87%（p<0.01）、40%（无统计学意义）和67%（p<0.01）]。
结论
在该模型中，罗氟司特抑制EAR，抑制AHR并减少炎症细胞浸润。
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