中文摘要：

目的了解十四环大环内酯类抗生素对气道黏液高分泌过程的调控作用及其可能的机制。方法大鼠气道内注入脂多糖（LPS）建立气道黏液高分泌模型。分别给予罗红霉素（1—10mg／kg）、交沙霉素（10mg／kg）和阿莫西林（40mg／kg）管喂4d。提取肺组织和支气管肺泡灌洗液（BALF），采用ELLA、ELISA、免疫组化、RT-PCR及Western Blot等方法检测炎性细胞因子[白细胞介素1β（IL-1β）、IL-8和肿瘤坏死因子-α（TNF-α）]、黏蛋白、Muc5ac和核因子-κB（NF-κB）等的表达水平。结果LPS刺激可以使大鼠气道上皮Muc5ac蛋白和mRNA表达增高，使BALF中性粒细胞增高、黏蛋白含量增多、炎性细胞因子（IL-1β、1L-8和TNF-α）表达增加。同时气道上皮细胞胞浆NF-κB表达和NF-κB入核率均增高。罗红霉素（5和10mg／kg）可以抑制由LPS导致的Muc5ac高表达和NF-κB的核内转移，抑制肺组织内中性粒细胞聚集和肺泡灌洗液中性粒细胞的数量以及炎性细胞因子水平。NF-κB的入核率与细胞因子、Muc5acn mRNA水平呈正相关关系。交沙霉素组和阿莫西林组未观察到类似结果。结论罗红霉素可以抑制LPS所致的肺组织炎症反应和气道黏液高分泌状态，其机制可能是部分通过抑制NF-κB活化、中性粒细胞聚集和炎性细胞因子释放而发挥作用。

英文摘要：

Objective To examine the effect of 14-membered ring macrolide antibiotics on airway mucus hypersecretion stimulated by lipopolysaccharide （LPS） in rats and its molecular mechanism. Methyls Rat airway mucus hypersecretion was induced by intratracheal instillation of LPS. Rats treated with or without LPS were orally administered with roxithromycin （1-10 mg/kg）, josamycin （10 mg/kg）, or amoxicillin （40 mg/kg） for 4 days. The mRNA and protein expression of Muc5ac and nuclear factor-κB in bronchial epithelia were detected by RT-PCR, immunohistochemistry and Western blot. Mucins, interleukin-1β（IL-1β）, IL-8 and tumor necrosing factor-α （TNF-α） in bronchoalveolar lavage fluid （BALF） were assayed with ELLA and ELISA. Results LPS significantly induced the expression of Muc5ac mRNA and protein in bronchial epithelia, and increased the concentration of mucins, IL-1β, IL-8 and TNF-α and neutrophil number in BALF. Moreover, LPS increased the staining of NF-κB in cytoplasm and nuclear translocation ratio in airway epithelial cells. The upregulated expression of Muc5ac mRNA was positively correlated with nuclear factor-kappa B（NF-κB） activation and cytokine concentration （P 〈 0.05）. Roxithromycin （5 and 10 mg/kg） significantly suppressed bronchial MucSac expression and NF-κB nuclear translocation stimulated by LPS and reduced the number of PMN, the concentration of mucins and inflammatory cytokines in BALF （ P 〈 0.05）. There were significant correlation between the ratio of NF-κB nuclear translocation and expression level of Muc5ac mRNA. Such effects were not observed in josamycin or amoxicillin group. Conclusions Roxithromycin inhibits pulmonary inflammatory response and airway mucus hypersecretion induced by LPS, which might be ascribed to inhibition of NF-κB activation, reduction of neutrophil infiltration and inflammatory cytokine release.