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首页> 外文期刊>COPD: Journal of Chronic Obstructive Pulmonary Disease >Roflumilast increases Clara cell secretory protein in cigarette smoke-exposed mice.
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Roflumilast increases Clara cell secretory protein in cigarette smoke-exposed mice.

机译：罗氟司特增加了香烟烟雾暴露小鼠的克拉拉细胞分泌蛋白。

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摘要

Decreased Clara cell secretory protein (CCSP) levels have been found in smokers and chronic obstructive pulmonary disease (COPD) patients, which may be related to the development of COPD. A phosphodiesterase-4 (PDE4) inhibitor, roflumilast, appears to have therapeutic value for COPD. However, its effect on CCSP in cigarette smoke (CS)-exposed lungs has not been investigated. AKR/J mice were treated as follows: air control, CS, roflumilast plus CS, and roflumilast. Mice underwent four weeks of air or CS exposure. Roflumilast was administrated at 5mg/kg via gavage once daily for the duration of the study. CCSP levels in bronchoalveolar lavage (BAL) fluid and ERK1/2 activation in lungs were examined. CS exposure tended to decrease CCSP levels in BAL fluid compared to air controls. Treatment with roflumilast significantly reversed CS-induced downward trend of CCSP in BAL fluid. Roflumilast significantly inhibited CS-induced upward trend of ERK1/2 activation in lungs, and the levels of activated ERK1/2 in lungs negatively correlated with CCSP levels of BAL fluid in CS, and CS plus roflumilast groups. Our results demonstrate that one of the therapeutic mechanisms of roflumilast is to reverse CS-induced downward trend in CCSP levels of BAL fluid, which may be mediated by down-regulating ERK1/2 activity.
机译：在吸烟者和慢性阻塞性肺疾病（COPD）患者中发现克拉拉细胞分泌蛋白（CCSP）水平降低，这可能与COPD的发生有关。磷酸二酯酶4（PDE4）抑制剂罗氟司特似乎对COPD具有治疗价值。但是，尚未研究其对接触香烟烟雾（CS）的肺中CCSP的影响。 AKR / J小鼠的治疗如下：空气对照，CS，罗氟司特加CS和罗氟司特。小鼠经历空气或CS暴露四个星期。在研究期间，每天通过管饲法给予罗氟司特5mg / kg。检查支气管肺泡灌洗（BAL）液中的CCSP水平和肺中的ERK1 / 2激活。与空气对照相比，CS暴露倾向于降低BAL液中的CCSP水平。罗氟司特治疗显着逆转了CS诱导的BAL液CCSP下降趋势。罗氟司特显着抑制CS诱导的肺中ERK1 / 2激活的上升趋势，并且CS和CS加罗氟司特组中肺中活化ERK1 / 2的水平与BAL液的CCSP水平负相关。我们的结果表明，罗氟司特的治疗机制之一是逆转CS诱导的BAL液CCSP水平下降趋势，这可能是通过下调ERK1 / 2活性来介导的。

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