1. Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model
- Author
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Guangxian Chen, Mengya Liang, Suiqing Huang, Huang Shaojie, Yuan Yue, Jian Hou, Huayang Li, Kangni Feng, Zhongkai Wu, and Xiaolin Huang
- Subjects
Cardiology ,Apoptosis ,030204 cardiovascular system & hematology ,Pharmacology ,Biochemistry ,General Biochemistry, Genetics and Molecular Biology ,Melatonin ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Autophagy ,Protein kinase B ,Mechanistic target of rapamycin ,PI3K/AKT/mTOR pathway ,Myocardial protection ,chemistry.chemical_classification ,Reactive oxygen species ,TUNEL assay ,biology ,business.industry ,General Neuroscience ,Cardiopulmonary bypass ,Cell Biology ,General Medicine ,surgical procedures, operative ,Terminal deoxynucleotidyl transferase ,chemistry ,biology.protein ,Medicine ,Creatine kinase ,General Agricultural and Biological Sciences ,business ,Zoology ,030217 neurology & neurosurgery ,medicine.drug - Abstract
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.
- Published
- 2021