Autophagy decreases alveolar macrophage apoptosis by attenuating endoplasmic reticulum stress and oxidative stress.
Autophagy decreases alveolar macrophage apoptosis by attenuating endoplasmic reticulum stress and oxidative stress.
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DOI：
10.18632/oncotarget.13560
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发表时间：
2016-12-27
期刊：
影响因子：
--
通讯作者：
Geng Q
中科院分区：
文献类型：
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作者：
Fan T;Chen L;Huang Z;Mao Z;Wang W;Zhang B;Xu Y;Pan S;Hu H;Geng Q
为了研究缺氧早期自噬对肺泡巨噬细胞凋亡的影响及其机制，我们建立了细胞缺氧复氧模型和原位左肺缺血再灌注模型。稳定表达RFP-LC 3的大鼠肺泡巨噬细胞用自噬抑制剂（3-甲基腺嘌呤，3-MA）或自噬促进剂（雷帕霉素）处理，然后在2 h、4 h或6 h后进行缺氧-复氧处理。将20只Sprague-Dawley雄性大鼠随机分为4组：左肺门无阻塞模型组：左肺门阻断1h，DMSO灌洗（对照组），用100 ml/kg 3-MA阻断左肺门1 h（5 μmol/L）灌洗（3-MA组），用100 ml/kg雷帕霉素（250 nmol/L）灌洗（雷帕霉素组）阻断左肺门1 h。雷帕霉素降低了未折叠的蛋白质反应，这减少了内质网应激介导的细胞凋亡在缺氧的存在。雷帕霉素增加超氧化物歧化酶活性和降低丙二醛水平，而3-MA降低超氧化物歧化酶活性和增加丙二醛水平。因此，在体外和体内缺氧早期，自噬通过减轻内质网应激和氧化应激来减少肺泡巨噬细胞凋亡。这可能代表了一种新的方法来保护肺缺血再灌注损伤。
To study the impact of autophagy on alveolar macrophage apoptosis and its mechanism in the early stages of hypoxia, we established a cell hypoxia-reoxygenation model and orthotopic left lung ischemia-reperfusion model. Rat alveolar macrophages stably expressing RFP-LC3 were treated with autophagy inhibitor (3-methyladenine, 3-MA) or autophagy promoter (rapamycin), followed by hypoxia-reoxygenation treatment 2 h, 4 h or 6 h later. Twenty Sprague-Dawley male rats were randomly divided into four different groups: no blocking of left lung hilum (model group), left lung hilum blocked for 1h with DMSO lavage (control group), left lung hilum blocked for 1 h with 100 ml/kg 3-MA (5 μmol/L) lavage (3-MA group), and left lung hilum blocked for 1 h with 100 ml/kg rapamycin (250 nmol/L) lavage (rapamycin group). Rapamycin decreased the unfolded protein response, which reduced endoplasmic reticulum stress-mediated apoptosis in the presence of oxygen deficiency. Rapamycin increased superoxide dismutase activities and decreased malondialdehyde levels, whereas 3-MA decreased superoxide dismutase activities and increased malondialdehyde levels. Thus, autophagy decreases alveolar macrophage apoptosis by attenuating endoplasmic reticulum stress and oxidative stress in the early stage of hypoxia in vitro and in vivo. This could represent a new approach to protecting against lung ischemia-reperfusion injury.