Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model
Background Myocardial injury is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to test the hypothesis that melatonin could attenuate myocardial injury in a rat CPB model. Methods Eighteen male Sprague-Dawley rats were randomly divided into three gro...
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doaj-a0ca9fd64ea74443b5229e77e4787a7e2021-04-17T15:05:11ZengPeerJ Inc.PeerJ2167-83592021-04-019e1126410.7717/peerj.11264Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass modelXiaolin Huang0Jian Hou1Suiqing Huang2Kangni Feng3Yuan Yue4Huayang Li5Shaojie Huang6Mengya Liang7Guangxian Chen8Zhongkai Wu9Department of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaBackground Myocardial injury is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to test the hypothesis that melatonin could attenuate myocardial injury in a rat CPB model. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups, n = 6 for each group: the sham operation (SO) group, CPB group and melatonin group. Rats in the SO group underwent cannulation without CPB, rats in CPB group intraperitoneal injected an equal volume of vehicle daily for 7 days before being subjected to CPB and rats in melatonin group intraperitoneal injected 20 mg/kg of melatonin solution daily for 7 days before being subjected to CPB. After 120 min for CPB, the expression levels of plasma interleukin (IL) -6, IL-1β, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), creatine kinase (CK) -MB and cardiac troponin T (cTnT) were measured. Reactive oxygen species (ROS) were detected by dihydroethidium (DHE). Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Mitochondrial damage and autophagosomes were detected by electron microscopy. Apoptosis inducing factor (AIF) was detected by immunofluorescence. The expression of B cell lymphoma/leukemia2 associated X (Bax), B cell lymphoma/leukemia 2 (Bcl-2), cytochrome C (Cyto-C), cleaved caspase-9, AKT, p-AKT, signal transducer and activator of transcription 3 (STAT3), p-STAT3, LC3, P62, mechanistic target of rapamycin kinase (mTOR), p-mTOR and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using western blotting. Results Melatonin significantly decreased the levels of IL-1β, IL-6, MDA, CK-MB and cTnT and increased the levels of SOD and GSH-Px, all of which were altered by CPB. Melatonin reduced cardiomyocyte superoxide production, the apoptosis index and autophagy in cardiomyocytes induced by CPB. The AKT, STAT3 and mTOR signaling pathways were activated by melatonin during CPB. Conclusion Melatonin may serve as a cardioprotective factor in CPB by inhibiting oxidative damage, apoptosis and autophagy. The AKT, STAT3 and mTOR signaling pathways were involved in this process.https://peerj.com/articles/11264.pdfCardiopulmonary bypassMelatoninMyocardial protectionApoptosisAutophagy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaolin Huang Jian Hou Suiqing Huang Kangni Feng Yuan Yue Huayang Li Shaojie Huang Mengya Liang Guangxian Chen Zhongkai Wu |
spellingShingle |
Xiaolin Huang Jian Hou Suiqing Huang Kangni Feng Yuan Yue Huayang Li Shaojie Huang Mengya Liang Guangxian Chen Zhongkai Wu Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model PeerJ Cardiopulmonary bypass Melatonin Myocardial protection Apoptosis Autophagy |
author_facet |
Xiaolin Huang Jian Hou Suiqing Huang Kangni Feng Yuan Yue Huayang Li Shaojie Huang Mengya Liang Guangxian Chen Zhongkai Wu |
author_sort |
Xiaolin Huang |
title |
Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model |
title_short |
Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model |
title_full |
Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model |
title_fullStr |
Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model |
title_full_unstemmed |
Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model |
title_sort |
melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model |
publisher |
PeerJ Inc. |
series |
PeerJ |
issn |
2167-8359 |
publishDate |
2021-04-01 |
description |
Background Myocardial injury is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to test the hypothesis that melatonin could attenuate myocardial injury in a rat CPB model. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups, n = 6 for each group: the sham operation (SO) group, CPB group and melatonin group. Rats in the SO group underwent cannulation without CPB, rats in CPB group intraperitoneal injected an equal volume of vehicle daily for 7 days before being subjected to CPB and rats in melatonin group intraperitoneal injected 20 mg/kg of melatonin solution daily for 7 days before being subjected to CPB. After 120 min for CPB, the expression levels of plasma interleukin (IL) -6, IL-1β, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), creatine kinase (CK) -MB and cardiac troponin T (cTnT) were measured. Reactive oxygen species (ROS) were detected by dihydroethidium (DHE). Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Mitochondrial damage and autophagosomes were detected by electron microscopy. Apoptosis inducing factor (AIF) was detected by immunofluorescence. The expression of B cell lymphoma/leukemia2 associated X (Bax), B cell lymphoma/leukemia 2 (Bcl-2), cytochrome C (Cyto-C), cleaved caspase-9, AKT, p-AKT, signal transducer and activator of transcription 3 (STAT3), p-STAT3, LC3, P62, mechanistic target of rapamycin kinase (mTOR), p-mTOR and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using western blotting. Results Melatonin significantly decreased the levels of IL-1β, IL-6, MDA, CK-MB and cTnT and increased the levels of SOD and GSH-Px, all of which were altered by CPB. Melatonin reduced cardiomyocyte superoxide production, the apoptosis index and autophagy in cardiomyocytes induced by CPB. The AKT, STAT3 and mTOR signaling pathways were activated by melatonin during CPB. Conclusion Melatonin may serve as a cardioprotective factor in CPB by inhibiting oxidative damage, apoptosis and autophagy. The AKT, STAT3 and mTOR signaling pathways were involved in this process. |
topic |
Cardiopulmonary bypass Melatonin Myocardial protection Apoptosis Autophagy |
url |
https://peerj.com/articles/11264.pdf |
work_keys_str_mv |
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