Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease
Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease
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DOI：
10.1038/ncomms3686
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发表时间：
2013-11-01
影响因子：
16.6
通讯作者：
Mizushima, Tohru
中科院分区：
文献类型：
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作者：
Tanaka, Ken-Ichiro;Ishihara, Tomoaki;Mizushima, Tohru
慢性阻塞性肺疾病（COPD）的临床治疗不仅需要通过支气管扩张改善气流，而且还需要通过控制炎症来抑制肺气肿。在这里，我们筛选了一个化合物库，包括临床使用的药物，以防止弹性蛋白酶诱导的小鼠空域扩大的能力。我们发现，鼻内给药或吸入用于治疗胃肠道疾病的毒蕈碱拮抗剂溴化甲哌唑酯，可降低弹性蛋白酶诱导的空域扩大和呼吸功能障碍的严重程度。尽管溴化甲哌唑酯显示支气管扩张活性，但大多数其他毒蕈碱拮抗剂不能改善弹性蛋白酶诱导的肺部疾病。除了抑制弹性蛋白酶诱导的肺部炎症反应和超氧阴离子的产生外，溴化甲哌唑酯还降低了香烟烟雾诱导的气道扩大和呼吸功能障碍的水平。基于这些结果，我们认为溴甲哌唑酯可能是一种有效的治疗慢性阻塞性肺疾病，由于其抗炎和支气管扩张活性。
The clinical treatment of chronic obstructive pulmonary disease (COPD) requires not only an improvement of airflow by bronchodilation but also the suppression of emphysema by controlling inflammation. Here we screen a compound library consisting of clinically used drugs for their ability to prevent elastase-induced airspace enlargement in mice. We show that intratracheal administration or inhalation of mepenzolate bromide, a muscarinic antagonist used to treat gastrointestinal disorders, decreases the severity of elastase-induced airspace enlargement and respiratory dysfunction. Although mepenzolate bromide shows bronchodilatory activity, most other muscarinic antagonists do not improve elastase-induced pulmonary disorders. Apart from suppressing elastase-induced pulmonary inflammatory responses and the production of superoxide anions, mepenzolate bromide reduces the level of cigarette smoke-induced airspace enlargement and respiratory dysfunction. Based on these results, we propose that mepenzolate bromide may be an effective therapeutic for the treatment of COPD due to its anti-inflammatory and bronchodilatory activities.