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噻托溴铵抑制 BALB/c 小鼠过敏性哮喘复发。

Tiotropium bromide inhibits relapsing allergic asthma in BALB/c mice.

机构信息

Division of Immunology, Allergy and Infectious Diseases, Experimental Allergy, Department of Dermatology, Medical University of Vienna, Vienna, Austria.

Department of Pulmonary Disease Research, Boehringer-Ingelheim Pharma, Biberach, Germany.

出版信息

Pulm Pharmacol Ther. 2014 Feb;27(1):44-51. doi: 10.1016/j.pupt.2013.09.004. Epub 2013 Sep 30.

Abstract

Recurrent relapses of allergic lung inflammation in asthmatics may lead to airway remodeling and lung damage. We tested the efficacy of tiotropium bromide, a selective long-acting, muscarinic receptor antagonist as an adjunct therapy in relapses of allergic asthma in mice. We compared the effectiveness of local intranasal administration of tiotropium and dexamethasone in acute and relapsing allergic asthma in BALB/c mice. Although tiotropium at low doses is a potent bronchodilator, we tested higher doses to determine effectiveness on inflammation and mucus hypersecretion. A 5-day course of twice daily intranasal tiotropium or dexamethasone (1 mg/kg (b.w.)) suppressed airway eosinophils by over 87% during disease initiation and 88% at relapse compared to vehicle alone. Both drugs were comparable in their capacity to suppress airway and parenchymal inflammation and mucus hypersecretion, though tiotropium was better than dexamethasone at reducing mucus secretion during disease relapse. Despite treatment with either drug, serum antigen-specific IgE or IgG1 antibody titres remained unchanged. Our study indicates that tiotropium at higher doses than required for bronchodilation, effectively suppresses inflammation and mucus hypersecretion in the lungs and airways of mice during the initiation and relapse of asthma. Tiotropium is currently not approved for use in asthma. Clinical studies have to demonstrate the efficacy of tiotropium in this respiratory disease.

摘要

哮喘患者的过敏肺炎症反复发作可能导致气道重塑和肺损伤。我们测试了噻托溴铵(一种选择性长效毒蕈碱受体拮抗剂)作为过敏性哮喘发作辅助治疗的疗效。我们比较了局部鼻腔内给予噻托溴铵和地塞米松在 BALB/c 小鼠急性和复发性过敏性哮喘中的效果。尽管低剂量的噻托溴铵是一种有效的支气管扩张剂,但我们测试了更高的剂量,以确定其对炎症和粘液分泌过多的效果。为期 5 天的每天两次鼻腔内给予噻托溴铵或地塞米松(1mg/kg(bw))在疾病开始时抑制气道嗜酸性粒细胞超过 87%,在复发时抑制 88%,而单独使用载体则无抑制效果。两种药物在抑制气道和实质炎症以及粘液分泌过多方面具有相似的效果,尽管噻托溴铵在缓解疾病复发时减少粘液分泌方面优于地塞米松。尽管使用了任何一种药物,血清抗原特异性 IgE 或 IgG1 抗体滴度均未改变。我们的研究表明,噻托溴铵在治疗支气管扩张的高剂量下,能有效抑制哮喘发作和复发时小鼠肺部和气道的炎症和粘液分泌过多。噻托溴铵目前尚未被批准用于哮喘治疗。临床研究必须证明噻托溴铵在这种呼吸道疾病中的疗效。

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