Abstract
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.
Highlights
Patients with diabetes often die from diabetes-related complications
The practical implications of diabetic lung are subclinical, patients with diabetes are vulnerable to severe respiratory derangements when they underwent an acute or chronic pulmonary and/or cardiac disease [2, 3]
There was no apparent pathologic alteration in the lung sections from the sham group in control or diabetic rats; after the rats subjected to myocardial ischemia reperfusion (IR) insult, acute lung injury (ALI) with intra-alveolar and interstitial edema, hemorrhage, and inflammatory cell infiltration was showed in the lung section
Summary
Patients with diabetes often die from diabetes-related complications. Impaired control of blood glucose may lead to pathological changes and functional damages in numerous tissues and organs, including the eye, kidney, cardiovascular system, and nerve tissue [1]. The pathogenesis of diabetic lung is implicated with hyperglycemia-induced oxidative stress and inflammatory reaction, which accelerate decline in respiratory function [3]. The practical implications of diabetic lung are subclinical, patients with diabetes are vulnerable to severe respiratory derangements when they underwent an acute or chronic pulmonary and/or cardiac disease [2, 3]. A serious type of cardiac diseases, is one of the leading causes of diabetic mortality [4]. Previous studies indicated that myocardial IR could cause injury in distant organs, and the lung can be one of the most affected organs [5, 6]. Further studies suggested that acute lung injury (ALI) induced by myocardial IR in diabetes was more serious than that in nondiabetics [7]. There are little relevant reports concerning the potential mechanism of ALI induced by myocardial IR under diabetic condition
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