阿奇霉素可以减轻过敏性哮喘模型小鼠非感染性气道炎症
2010/01/07
关键词：酶联免疫吸附试验；白介素；巨噬细胞阻断蛋白；碘酸希夫；磷酸盐缓冲液。
背景：大环内酯类抗生素对哮喘的治疗效果是否基于其抗炎作用目前还难以定论，因为其疗效可能与其抗感染作用相关。本文假设阿奇霉素有直接的抗炎作用，并利用非感染性过敏性哮喘小鼠模型进行了验证。
方法：选择7周龄的BALB/cJ小鼠，在试验开始的0～7天通过腹腔注射卵白蛋白致敏小鼠，第11天经鼻激发，诱发过敏性气道炎症。在第13～16天给予阿奇霉素或磷酸盐缓冲液（PBS）治疗。第17天计数气道内白细胞，测定支气管肺泡灌洗液（BALF）中多种炎症介质表达，粘液细胞化生以评价气道炎症。另一组试验小鼠在激发后给予阿奇霉素或PBS治疗。每项试验均重复3次（每组总计9-11只小鼠）。
结果：与PBS治疗组相比，阿奇霉素可减轻OVA所导致的气道炎症，肺组织及BALF中总白细胞数下降，阿奇霉素还可抑制BALF中细胞因子的表达（如IL-13,IL-5）及趋化因子（CCL2,CCL3,CCL4）表达，削减粘液细胞化生的程度。OVA激发后立即给予阿奇霉素也有同样的疗效。
结论：阿奇霉素可抑制非感染性过敏性哮喘模型小鼠的过敏性气道炎症。此结果证实了阿奇霉素的抗炎作用，提示阿奇霉素可用于治疗包括哮喘在内的非感染性气道炎症性疾病。
（马艳良 北京大学人民医院呼吸科 100044 摘译）
（Chest August 2009 136:498-506）
Azithromycin Attenuates Airway Inflammation in a Noninfectious Mouse Model of Allergic Asthma
Background: Definitive conclusions regarding the antiinflammatory effects of macrolide antibiotics for treatment of asthma are difficult to formulate since their beneficial effects may be related to their antimicrobial action. We hypothesized that azithromycin possesses distinct antiinflammatory properties and tested this assumption in a noninfectious mouse model of allergic asthma.
Methods: To induce allergic airway inflammation, 7-week-old BALB/cJ mice underwent intraperitoneal ovalbumin sensitization on days 0 and 7 followed by an intranasal challenge on day 14. Mice were treated with azithromycin or phosphate-buffered saline (PBS) solution on days 13 through 16. On day 17, airway inflammation was assessed by quantifying leukocytes in the airway, expression of multiple inflammatory mediators in the BAL fluid, and mucous cell metaplasia. In a separate set of experiments, azithromycin or PBS solution treatment were initiated after the ovalbumin challenge. Each experiment was repeated 3 times (a total of 9 to 11 mice in each group).
Results: Compared to treatment with PBS solution, azithromycin attenuated the ovalbumin-dependent airway inflammation. We observed a decrease in total leukocytes in the lung tissue and BAL fluid. In addition, azithromycin attenuated the expression of cytokines (eg, interleukin [IL]-13 and IL-5) and chemokines (eg, CCL2, CCL3, and CCL4) in the BAL fluid and abrogated the extent of mucous cell metaplasia. Similar antiinflammatory effects were observed when azithromycin treatment was initiated after the ovalbumin challenge.
Conclusion: In this noninfectious mouse model of allergic asthma, azithromycin attenuated allergic airway inflammation. These findings demonstrate an antiinflammatory effect of azithromycin and suggest azithromycin may have beneficial effects in treating noninfectious airway inflammatory diseases, including asthma.
Chest August 2009 136:498-506
