Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy.
Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy.
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DOI：
10.1183/09031936.00042512
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Pinkerton KE
中科院分区：
文献类型：
--
作者：
Davis BB;Zeki AA;Bratt JM;Wang L;Filosto S;Walby WF;Kenyon NJ;Goldkorn T;Schelegle ES;Pinkerton KE
慢性阻塞性肺疾病（COPD）是第三大死亡原因。他汀类药物可能对COPD等呼吸系统疾病具有治疗潜力，但它们是否能预防支气管上皮损伤尚不清楚。我们假设辛伐他汀减轻急性烟草烟雾诱导的嗜酸性肺炎症和气道上皮损伤。自发性高血压大鼠给予辛伐他汀（20 mg·kg-1 i. p.）在烟草烟雾暴露前7天和烟雾暴露3天期间，或仅在烟草烟雾暴露期间，每天一次。在烟雾暴露之前和整个暴露过程中，辛伐他汀预处理可减少白细胞、中性粒细胞和巨噬细胞流入肺和气道的总量。辛伐他汀减弱烟草烟雾诱导的细胞浸润到肺实质和气道上皮下和间质空间。1周的辛伐他汀预处理几乎完全阻止了烟雾诱导的气道上皮层剥脱，而辛伐他汀仅与烟雾暴露同时给药没有效果。辛伐他汀可能是治疗吸烟引起的肺部疾病（例如COPD）的一种新型辅助治疗方法。考虑到他汀类药物预处理的需要，可能存在一个关键的调节过程，这是他汀类药物抗炎作用所必需的。未来的工作需要阐明这种他汀类药物保护作用的机制。
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death. The statin drugs may have therapeutic potential in respiratory diseases such as COPD, but whether they prevent bronchial epithelial injury is unknown. We hypothesised that simvastatin attenuates acute tobacco smoke-induced neutrophilic lung inflammation and airway epithelial injury. Spontaneously hypertensive rats were given simvastatin (20 mg·kg−1 i.p.) daily for either 7 days prior to tobacco smoke exposure and during 3 days of smoke exposure, or only during tobacco smoke exposure. Pre-treatment with simvastatin prior to and continued throughout smoke exposure reduced the total influx of leukocytes, neutrophils and macrophages into the lung and airways. Simvastatin attenuated tobacco smoke-induced cellular infiltration into lung parenchymal and airway subepithelial and interstitial spaces. 1 week of simvastatin pre-treatment almost completely prevented smoke-induced denudation of the airway epithelial layer, while simvastatin given only concurrently with the smoke exposure had no effect. Simvastatin may be a novel adjunctive therapy for smoke-induced lung diseases, such as COPD. Given the need for statin pre-treatment there may be a critical process of conditioning that is necessary for statins’ anti-inflammatory effects. Future work is needed to elucidate the mechanisms of this statin protective effect.
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影响因子：
5.8
作者：
Hsu HH;Ko WJ;Hsu JY;Chen JS;Lee YC;Lai IR;Chen CF
通讯作者：
Chen CF
DOI：
10.1016/j.bbrc.2011.06.008
发表时间：
2011-07-08
影响因子：
3.1
作者：
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Pinkerton, Kent E.
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作者：
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通讯作者：
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影响因子：
5.3
作者：
Eccles, Kirstie A.;Sowden, Heather;Graham, Anne M.
通讯作者：
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影响因子：
5.6
作者：
Chen, Ya-Juan;Chen, Peng;Wen, Fu-Qiang
通讯作者：
Wen, Fu-Qiang