The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats

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...

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Main Authors: Liying Zhan, Yuan Zhang, Wating Su, Qiongxia Zhang, Rong Chen, Bo Zhao, Wei Li, Rui Xue, Zhongyuan Xia, Shaoqing Lei
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2018/5047526
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author Liying Zhan
Yuan Zhang
Wating Su
Qiongxia Zhang
Rong Chen
Bo Zhao
Wei Li
Rui Xue
Zhongyuan Xia
Shaoqing Lei
author_facet Liying Zhan
Yuan Zhang
Wating Su
Qiongxia Zhang
Rong Chen
Bo Zhao
Wei Li
Rui Xue
Zhongyuan Xia
Shaoqing Lei
author_sort Liying Zhan
collection DOAJ
description 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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spelling doaj-art-e4060f6363e5450e97607d1319fdede22025-02-03T01:03:32ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/50475265047526The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic RatsLiying Zhan0Yuan Zhang1Wating Su2Qiongxia Zhang3Rong Chen4Bo Zhao5Wei Li6Rui Xue7Zhongyuan Xia8Shaoqing Lei9Department of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan, ChinaPatients 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.http://dx.doi.org/10.1155/2018/5047526
spellingShingle Liying Zhan
Yuan Zhang
Wating Su
Qiongxia Zhang
Rong Chen
Bo Zhao
Wei Li
Rui Xue
Zhongyuan Xia
Shaoqing Lei
The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats
Journal of Diabetes Research
title The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats
title_full The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats
title_fullStr The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats
title_full_unstemmed The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats
title_short The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats
title_sort roles of autophagy in acute lung injury induced by myocardial ischemia reperfusion in diabetic rats
url http://dx.doi.org/10.1155/2018/5047526
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