To investigate whether miR-124-3p influences cell apoptosis, inflammatory response, and oxidative stress in rats with acute myocardial infarction (AMI) by mediating the SIRT1/FGF21/CREB/PGC1α pathway. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-124-3p and SIRT1. AMI rats were established via coronary artery ligation after injection with agomiR-124-3p, antagomiR-124-3p, and/or SIRT1 siRNA, and triphenyltetrazolium chloride (TTC), HE, and TUNEL stainings were performed. Bio-Plex rat cytokine assays were performed to determine proinflammatory factor levels. qRT-PCR and Western blotting were used to examine the mRNA and protein expression, respectively. The activity levels of antioxidant enzymes in myocardial tissues were also measured. miR-124-3p was confirmed to target SIRT1 in the H9C2 cells. AMI rats exhibited increased miR-124-3p expression and decreased SIRT1 expression in myocardial tissues. HE staining showed a disorganized cell arrangement and inflammatory cell infiltration in the myocardial tissues of the AMI rats, which was more severe in the rats injected with SIRT1 and agomiR-124-3p but was ameliorated in those treated with antagomiR-124-3p. Moreover, the AMI rats in the antagomiR-124-3p group presented with a reduction in infarct area with an increase in antioxidant enzyme activity, Bcl-2 expression, and activation of the FGF21/CREB/PGC1α pathway, as well as a decrease in cell apoptosis rate, Bax and Caspase-3 expression, and levels of proinflammatory factors, effects that were reversed by si-SIRT1. Inhibiting miR-124-3p expression may activate the FGF21/CREB/PGC1α pathway to reduce cell apoptosis, alleviate the inflammatory response, and attenuate oxidative stress in AMI rats by targeting SIRT1. Graphical abstract.
Keywords: AMI; FGF21/CREB/PGC1α; SIRT1; miR-124-3p.
© 2021. University of Navarra.