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自噬通过缓解血气屏障损伤避免缺血再灌注损伤诱导的肺损伤

Autophagy protects against ischemia/reperfusion-induced lung injury through alleviating blood-air barrier damage

来源:Scopus 发布时间:2015-7-22
作者:Zhang, D., Li, C, Zhou, J., Song, Y., Fang, X., Ou, J., Li, J., Bai, C.
机构: 复旦大学附属中山医院胸外科
期刊: J HEART LUNG TRANSPL 2015年6月5期34卷

BACKGROUND: Understanding the role and underlying regulation mechanism of autophagy in ischemia/reperfusion (I/R)-induced lung injury may provide potentially new pharmacologic targets for treatment of acute lung injury. The aim of this study was to adjust autophagy with pharmacologic tagents to determine its functional significance in I/R-induced lung injury. METHODS: Human pulmonary microvascular endothelial cells (HPMVECs) and mice were preconditioned with autophagy inhibitor chloroquine or promoter rapamycin before they were challenged with oxygen-glucose deprivation/oxygen-glucose restoration (OGD) and lung I/R, respectively. Extracellular signal-regulated kinase (ERK)1/2 inhibitor U0126 was pre-injected into I/R-induced mice to test the role of ERK1/2 in regulating autophagy. RESULTS: OGD caused tight conjunction damage and cell death in HPMVECs, which was further aggravated by blocking autophagy, yet ameliorated through promoting autophagy. On a consistent basis, inhibiting autophagy aggravated I/R-induced lung edema and tissue inflammation, which was significantly alleviated by promoting autophagy with rapamycin. In addition, inhibition of ERK1/2 increased expression of active mammalian target-of-rapamycin and thus decreased I/R-induced autophagy. CONCLUSIONS: It appears that autophagy plays a protective role in I/R-induced lung injury and this effect may be enhanced by moderately improving autophagy level. Meanwhile, the ERK1/2 signal pathway has a positively regulating role in lung I/R-induced autophagy. © 2015 International Society for Heart and Lung Transplantation. All rights reserved.

 

通讯作者:Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Xuhui District, Shanghai, China
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