Abstract
IntroductionThis study’s objective is to investigate the effect of downregulation of micro ribonucleic acid (miR)-124a on myocardial injury after ischemia reperfusion (I/R) in rats.MethodsSprague Dawley (SD) rats (n=20) were divided into four groups - sham, I/R, I/R+miR-124a antagomir (I/R+ant-miR-124a), and I/R+ant-normal control (NC). The pathomorphological and infarct size variance of injured myocardial tissues with IR were conducted with hematoxylin (HE) and triphenyltetrazolium chloride (TTC) staining. The expression levels of miR-124a, BAX, nuclear factor kappa B (NF-KB), Notch1, and Hes1 were examined by quantitative real-time polymerase chain reaction or Western blot in myocardium. The inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α) were detected by the enzyme-linked immunosorbent assay, as well as the activity of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum by colorimetry.ResultsThe expression of miR-124a was increased in the I/R group. Compared with I/R and I/R+ant-NC groups, after downregulating miR-124a, the expression of IL-6, IL-1β, TNF-α, BAX, NF-KB, LDH, and CK were decreased, but the expression of Notch1 and Hes1 were increased. In HE staining, myocardial tissue edema, red blood cell exudation, and myocardial fiber arrangement disorder were accompanied by inflammatory cell infiltration and local necrosis in the I/R group. However, the pathological injury of myocardial tissue was alleviated after downregulating miR-124a. Additionally, TTC results showed that the myocardial infarction area was decreased in the I/R+ant-miR-124a group.ConclusionDownregulation of miR-124a expression through Notch pathway can significantly reduce myocardial damage after 24 hours of I/R in SD rats. Therefore, miR-124a may become a potential therapeutic target for I/R injury.
Highlights
This study’s objective is to investigate the effect of downregulation of micro ribonucleic acid-124a on myocardial injury after ischemia reperfusion (I/R) in rats
We found that micro ribonucleic acid (miR)-124a can regulate lipopolysaccharide-induced septic cardiac dysfunction by targeting STX2[12]
triphenyltetrazolium chloride (TTC) staining results showed that 24 hours after I/R, myocardial tissue in I/R group and I/R+ant-normal control (NC) group showed large-area infarction, with infarction areas of 42.32±3.58% and 39.56±3.22%, respectively, significantly increased compared with 5.82±2.78% in the control group (P
Summary
This study’s objective is to investigate the effect of downregulation of micro ribonucleic acid (miR)-124a on myocardial injury after ischemia reperfusion (I/R) in rats. There is no effective treatment to protect the heart from myocardial ischemia reperfusion (I/R). Once ligands normally located on the surface of adjacent cells were activated, the receptor transmits the signal to the nucleus through intracellular proteolysis and intracellular domain release[3]. This event caused the transcriptional activation complex to form and cause transcription of downstream target genes of Notch, such as Hes1[4]
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