Abstract
Oxidative stress plays a critical role in the progression of myocardial injury. Increasing evidence suggests that hiruidin can treat patients with cardio-injury. However, the mechanism of hirudin against myocardial infraction remains unknown. In the present study, we evaluated the potential role and mechanism of hirudin on both isoproterenol (ISO)-induced myocardial infraction (MI) in rats and Hypoxia-Reoxygenation model in H9C2 cells. Compared with the model group, hirudin apparently decreased the levels of myocardial Creatine Kinase Isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), and alleviated myocardial histopathological changes induced by ISO injection. The underlying mechanisms were revealed by the following observations: Hirudin exerted its cardioprotective effect via restoring super oxide dismutase (SOD), attenuating reactive oxygen species (ROS) and malondialdehyde (MDA). It induced the activation of Nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway through disrupting Keap1-Nrf2 complex, thus Nrf2 translocated from cytoplasm to nucleus to regulate Nrf2-dependent gene (HO-1, SOD) expressions. Furthermore, it should be noted that hirudin restored mitochondrial membrane potential in addition to cytochrome C-related apoptosis.
Keywords:
Apoptosis; Hirudin; Myocardial infarction; Nrf2; Oxidative stress.
Copyright © 2020. Published by Elsevier B.V.
MeSH terms
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Animals
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Apoptosis / drug effects*
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Cardiotonic Agents / pharmacology*
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Cell Hypoxia / drug effects
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Cell Line
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Cell Survival / drug effects
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Creatine Kinase, MB Form / blood
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Cytochromes c / metabolism
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Heme Oxygenase (Decyclizing) / genetics
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Heme Oxygenase (Decyclizing) / metabolism
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Hirudins / metabolism
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Hirudins / pharmacology*
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Isoproterenol / toxicity
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Kelch-Like ECH-Associated Protein 1 / metabolism
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L-Lactate Dehydrogenase / blood
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Male
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Malondialdehyde / blood
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Malondialdehyde / metabolism
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Membrane Potential, Mitochondrial / drug effects
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Myocardial Infarction / chemically induced
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Myocardial Infarction / drug therapy
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Myocardial Infarction / pathology
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Myocardial Infarction / prevention & control*
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Myocardium / cytology
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Myocardium / enzymology
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Myocardium / metabolism
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Myocardium / pathology
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NF-E2-Related Factor 2 / metabolism*
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Oxidative Stress / drug effects*
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Rats
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Reactive Oxygen Species / metabolism
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Signal Transduction / drug effects*
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Signal Transduction / genetics
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Superoxide Dismutase / blood
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism
Substances
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Cardiotonic Agents
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Hirudins
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KEAP1 protein, rat
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Kelch-Like ECH-Associated Protein 1
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NF-E2-Related Factor 2
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Nfe2l2 protein, rat
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Reactive Oxygen Species
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Malondialdehyde
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Cytochromes c
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L-Lactate Dehydrogenase
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Heme Oxygenase (Decyclizing)
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Hmox1 protein, rat
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Superoxide Dismutase
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Creatine Kinase, MB Form
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Isoproterenol