The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats.
The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats.
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自噬在糖尿病大鼠心肌缺血再灌注所致急性肺损伤中的作用
DOI：
10.1155/2018/5047526
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发表时间：
2018
影响因子：
4.3
通讯作者：
Lei S
中科院分区：
文献类型：
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作者：
Zhan L;Zhang Y;Su W;Zhang Q;Chen R;Zhao B;Li W;Xue R;Xia Z;Lei S
糖尿病患者易发生心肌缺血再灌注（IR）损伤，同时由于循环中活性氧（ROS）和炎症细胞因子的过度积累，可导致急性肺损伤（ALI）。尽管自噬在糖尿病和肺IR损伤中起重要作用，但自噬在继发于糖尿病心肌IR的ALI中的作用仍然很难理解。本研究旨在探讨糖尿病大鼠心肌缺血再灌注后肺组织自噬状态及其在氧化应激和炎症反应中的作用。阻断冠状动脉左前降支30 min，再灌注120 min。与对照组相比，糖尿病大鼠心肌缺血再灌注后肺损伤程度加重，肺损伤评分和湿/干比值升高，PaO 2降低，肺组织自噬功能受损，表现为LC-3 II/LC-3 I比值和Beclin-1表达降低，超氧化物歧化酶（SOD）活性降低，15-F2 t-异前列腺素生成增加。以及BAL液中白细胞计数和促炎细胞因子水平的增加。用Rap改善自噬显著减弱了所有这些变化，但自噬抑制剂3-MA表现出与Rap相反的不利或相反的作用。总之，糖尿病肺更容易受到心肌IR的影响，这与自噬受损有关。改善自噬可能通过抑制炎症反应和氧化应激而减轻糖尿病大鼠心肌IR所致的ALI。
Patients with diabetes are vulnerable to myocardial ischemia reperfusion (IR) injury, which may also induce acute lung injury (ALI) due to overaccumulation of reactive oxygen species (ROS) and inflammation cytokine in circulation. Despite autophagy plays a significant role in diabetes and pulmonary IR injury, the role of autophagy in ALI secondary to myocardial IR in diabetes remains largely elusive. We aimed to investigate pulmonary autophagy status and its roles in oxidative stress and inflammation reaction in lung tissues from diabetic rats subjected to myocardial IR. Control or diabetic rats were either treated with or without autophagy inducer rapamycin (Rap) or autophagy inhibitor 3-methyladenine (3-MA) before myocardial IR, which was achieved by occluding the left anterior descending coronary artery for 30 min and followed by reperfusion for 120 min. Diabetic rats subjected to myocardial IR showed more serious ALI with higher lung injury score and WET/DRY ratio and lower PaO2 as compared with control rats, accompanied with impaired autophagy indicated by reduced LC-3II/LC-3I ratio and Beclin-1 expression, decreased superoxide dismutase (SOD) activity, and increased 15-F2t-Isoprostane formation in lung tissues, as well as increased levels of leukocyte count and proinflammatory cytokines in BAL fluid. Improving autophagy with Rap significantly attenuated all these changes, but the autophagy inhibitor 3-MA exhibited adverse or opposite effects as Rap. In conclusion, diabetic lungs are more vulnerable to myocardial IR, which are involved in impaired autophagy. Improving autophagy could attenuate ALI induced by myocardial IR in diabetic rats, possibly through inhibiting inflammatory reaction and oxidative stress.
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影响因子：
--
作者：
Fan T;Chen L;Huang Z;Mao Z;Wang W;Zhang B;Xu Y;Pan S;Hu H;Geng Q
通讯作者：
Geng Q
DAMP 诱导的自噬通过促进 TRAF6 泛素化促进缺血再灌注损伤肺部的炎症反应。
影响因子：
12.4
作者：
Liu X;Cao H;Li J;Wang B;Zhang P;Dong Zhang X;Liu Z;Yuan H;Zhan Z
通讯作者：
Zhan Z
链脲佐菌素糖尿病小鼠缺氧引起的急性肺损伤加重。
影响因子：
1.7
作者：
Wang, Lu-Mei;Zhong, Nan-Zhe;Liu, Yu-Jian
通讯作者：
Liu, Yu-Jian
缺血后处理中自噬的激活有助于对大鼠心脏缺血/再灌注损伤的心脏保护作用
影响因子：
3
作者：
Wei, Chao;Li, Hongxia;Yang, Xiangjun
通讯作者：
Yang, Xiangjun
影响因子：
2.2
作者：
Alkan, Metin;Celik, Ali;Kavutcu, Mustafa
通讯作者：
Kavutcu, Mustafa