Role of toll‐like receptor 4 in melatonin‐induced cardioprotection

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74

作者:

F NduhirabandiK LamontZ AlbertynLH OpieS Lecour

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摘要:

p>Melatonin protects the heart against myocardial ischemia/reperfusion injury via the activation of the survivor activating factor enhancement (SAFE) pathway which involves tumor necrosis factor alpha (TNF α ) and the signal transducer and activator of transcription 3 (STAT3). Toll-like receptor 4 (TLR4) plays a crucial role in myocardial ischemia/reperfusion injury and activates TNF α . In this study, we investigated whether melatonin may target TLR4 to activate the SAFE pathway. Isolated hearts from rats or mice were subjected to ischemia/reperfusion injury. Melatonin (75 ng/L) and/or TAK242 (a specific inhibitor of TLR4 signaling, 500 n m ) were administered to the rat hearts before the induction of ischemia. Pre-ischemic myocardial STAT3 was evaluated by Western blotting. Lipopolysaccharide (LPS, a stimulator of TLR4) was administered to wild type, TNFα receptor 2 knockout or cardiomyocyte-specific STAT3-deficient mice (2.8 mg/kg, i.p) 45 min before the heart isolation. Myocardial infarct size was measured as an endpoint. Compared to the control, administration of melatonin reduced myocardial infarct size (34.7 ± 2.8% versus 62.6 ± 2.7%, P

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DOI:

10.1111/jpi.12286

被引量:

33

年份:

2016

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