Autophagy decreases alveolar epithelial cell injury by regulating the release of inflammatory mediators |
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Authors: | Tao Fan Shuo Yang Zhixin Huang Wei Wang Xiaobo Guo Shize Pan Boyou Zhang Yao Xu Yifan Fang Zhangfan Mao Hao Hu Qing Geng |
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Affiliation: | 1. Department of Thoracic Surgery, Renmin Hospital, Wuhan University, Wuhan, China;2. Department of Cardiology, Renmin Hospital, Cardiovascular Research Institute of Wuhan University, Wuhan University, Wuhan, China;3. Department of Gynecology and Obstetrics, Renmin Hospital, Wuhan University, Wuhan, China;4. Department of Emergency, Beijing Ji Shui Tan Hospital, Beijing, China |
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Abstract: | To research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in the early stages of hypoxia, we established a cell hypoxia–reoxygenation model and orthotopic left lung ischemia–reperfusion model. Rat alveolar epithelial cells stably expressing GFP-LC3 were treated with an autophagy inhibitor (3-MA) or an autophagy promoter (rapamycin), followed by hypoxia–reoxygenation treatment for 2, 4, and 6 hr in vitro. In vivo, 20 male Sprague Dawley rats were randomly divided into four groups (model group: No blocking of the hilum in the left lung; control group: Blocking of the hilum in the left lung for 1 hr with dimethyl sulfoxide lavage; 3-MA group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of 3-MA (5 μmol/L) solution lavage; and rapamycin group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of rapamycin (250 nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the nuclear factor kappa B signaling pathway and limited the expression of proinflammatory factors. A contrary result was found after the 3-MA pretreatment. These findings indicate that autophagy reduces ischemia–reperfusion injury by repressing inflammatory signaling pathways in the early stages of hypoxia in vitro and in vivo. Autophagy could be a new protective method for application in lung ischemia–reperfusion injury. |
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Keywords: | alveolar epithelial cell autophagy hypoxia–reoxygenation (H/R) inflammation ischemia–reperfusion (I/R) |
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