Melatonin Alleviates Ischemia-reperfusion Injury of Myocardial Cells by NLRP3 In-flammasome Activation Blockade via SIRT1
Objective:To investigate effect and mechanism of melatonin(Mel)on ischemia/reperfusion injury(IRI)of myocardial cells.Methods:H9C2 myocardial cells were selected to establish oxygen-glucose deprivation/reoxy-genation(OGD/R)model.H9C2 cardiomyocytes were randomized into four groups:1)NC group;2)OGD/R;3)OGD/R+Mel;4)OGD/R+Mel+EX527.The levels of LDH,proliferation activity,apoptosis,intracellular ROS levels,as well as the expression levels of related pathway proteins such as SIRT1,NLRP3,Caspase-1,IL-1β,TLR-4,NF-κB and TXNIP in each group of cells were detected.Results:Compared with the NC group,the levels of LDH in the culture me-dium,IL-1β in the supernatant,intracellular ROS levels,the apoptotic cells in the OGD/R group were significantly in-creased,while the cell proliferative viability was significantly reduced.The expression level of TLR4,NF-κB,TXNIP,NLRP3,Caspase-1 and IL-1β were significantly higher but lower SIRT1 expression(P<0.01).Compared to OGD/R group,the OGD/R+Mel group showed a significant decrease in LDH,IL-1 β,ROS,and apoptotic cells but higher cell proliferative viability.The expression level of TLR4,NF-κB,TXNIP,NLRP3,Caspase-1 and IL-1β were significantly lower accompany with higher expression of SIRT1.However,the protein expression trend was significantly reversed in OGD/R+Mel+EX527 again(P<0.01).Conclusion:Melatonin alleviates IRI of myocardial cells by NLRP3 inflamma-some activation blockade via up-regulation of SIRT1,which may secondary inhibit TLR4/NF-κB and ROS/TXNIP inflam-masome signaling pathway.
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