Role of toll‐like receptor 4 in melatonin‐induced cardioprotection
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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关键词：
cardioprotection ischemia/reperfusion injury melatonin survivor activating factor enhancement pathway toll‐like receptor 4
DOI：
10.1111/jpi.12286
被引量：
年份：
2016
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