Li Yunxiao, Yu Ganggang, Yuan Shaopeng, Tan Chunting, Lian Puqiao, Fu Lixia, Hou Qi, Xu Bo, Wang Haoyan
The Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Xichen District, Beijing, 100050, China.
Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Inflammation. 2017 Apr;40(2):497-510. doi: 10.1007/s10753-016-0495-z.
Cigarette smoke (CS) increases the risk of chronic obstructive pulmonary disease (COPD) by causing inflammation, emphysema, and reduced lung function. Additionally, CS can induce autophagy which contributes to COPD. Arachidonic acid-derived epoxyeicosatrienoic acids (EETs) have promising anti-inflammatory properties that may protect the heart and liver by regulating autophagy. For this reason, the effect of decreased soluble epoxide hydrolase (sEH, Ephx2)-mediated EET hydrolysis on inflammation, emphysema, lung function, and autophagy was here studied in CS-induced COPD in vivo. Adult male wild-type (WT) C57BL/6J and Ephx2 mice were exposed to air or CS for 12 weeks, and lung inflammatory responses, air space enlargement (emphysema), lung function, and autophagy were assessed. Lungs of Ephx2 mice had a less pronounced inflammatory response and less autophagy with mild distal airspace enlargement accompanied by restored lung function and steady weight gain. These findings support the idea that Ephx2 may hold promise as a therapeutic target for COPD induced by CS, and it may be protective property by inhibiting autophagy.
香烟烟雾（CS）通过引发炎症、肺气肿和肺功能下降，增加了慢性阻塞性肺疾病（COPD）的风险。此外，CS可诱导自噬，这也会导致COPD。花生四烯酸衍生的环氧二十碳三烯酸（EETs）具有良好的抗炎特性，可能通过调节自噬来保护心脏和肝脏。因此，本研究在体内CS诱导的COPD模型中，探讨了可溶性环氧化物水解酶（sEH，Ephx2）介导的EET水解减少对炎症、肺气肿、肺功能和自噬的影响。成年雄性野生型（WT）C57BL/6J小鼠和Ephx2小鼠暴露于空气或CS中12周，然后评估肺部炎症反应、气腔扩大（肺气肿）、肺功能和自噬情况。Ephx2小鼠的肺部炎症反应较轻，自噬较少，远端气腔轻度扩大，同时肺功能恢复，体重稳步增加。这些发现支持了这样一种观点：Ephx2有望成为CS诱导COPD的治疗靶点，并且它可能通过抑制自噬而具有保护作用。
