MicroRNA-124a Protects the Myocardium Against Ischemia Reperfusion Injury Through Regulation of the Notch Signaling Pathway

Abstract Introduction: 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. Methods: Sprague Dawley (SD) rats (n=20) were divided into four groups - sham, I/R, I/R+miR-124a antagomi...

Full description

Bibliographic Details
Main Authors: Weijun Xu, Shan Jiang, Qi Liu
Format: Article
Language:English
Published: Sociedade Brasileira de Cirurgia Cardiovascular 2021-12-01
Series:Brazilian Journal of Cardiovascular Surgery
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-76382021005008205&tlng=en
_version_ 1817991579580760064
author Weijun Xu
Shan Jiang
Qi Liu
author_facet Weijun Xu
Shan Jiang
Qi Liu
author_sort Weijun Xu
collection DOAJ
description Abstract Introduction: 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. Methods: Sprague 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. Results: The 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. Conclusion: Downregulation 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.
first_indexed 2024-04-14T01:15:11Z
format Article
id doaj.art-a7fe55714d264db68de95b031e9da099
institution Directory Open Access Journal
issn 1678-9741
language English
last_indexed 2024-04-14T01:15:11Z
publishDate 2021-12-01
publisher Sociedade Brasileira de Cirurgia Cardiovascular
record_format Article
series Brazilian Journal of Cardiovascular Surgery
spelling doaj.art-a7fe55714d264db68de95b031e9da0992022-12-22T02:20:54ZengSociedade Brasileira de Cirurgia CardiovascularBrazilian Journal of Cardiovascular Surgery1678-97412021-12-0110.21470/1678-9741-2020-0357MicroRNA-124a Protects the Myocardium Against Ischemia Reperfusion Injury Through Regulation of the Notch Signaling PathwayWeijun XuShan JiangQi Liuhttps://orcid.org/0000-0002-4337-5289Abstract Introduction: 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. Methods: Sprague 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. Results: The 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. Conclusion: Downregulation 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-76382021005008205&tlng=enMicroRNAs. Staining and Labeling. Myocardial Infarctation. Reperfusion. Tumor Necrosis Factor-alpha. Down-Regulation. RatsSprague-Dawley
spellingShingle Weijun Xu
Shan Jiang
Qi Liu
MicroRNA-124a Protects the Myocardium Against Ischemia Reperfusion Injury Through Regulation of the Notch Signaling Pathway
Brazilian Journal of Cardiovascular Surgery
MicroRNAs. Staining and Labeling. Myocardial Infarctation. Reperfusion. Tumor Necrosis Factor-alpha. Down-Regulation. Rats
Sprague-Dawley
title MicroRNA-124a Protects the Myocardium Against Ischemia Reperfusion Injury Through Regulation of the Notch Signaling Pathway
title_full MicroRNA-124a Protects the Myocardium Against Ischemia Reperfusion Injury Through Regulation of the Notch Signaling Pathway
title_fullStr MicroRNA-124a Protects the Myocardium Against Ischemia Reperfusion Injury Through Regulation of the Notch Signaling Pathway
title_full_unstemmed MicroRNA-124a Protects the Myocardium Against Ischemia Reperfusion Injury Through Regulation of the Notch Signaling Pathway
title_short MicroRNA-124a Protects the Myocardium Against Ischemia Reperfusion Injury Through Regulation of the Notch Signaling Pathway
title_sort microrna 124a protects the myocardium against ischemia reperfusion injury through regulation of the notch signaling pathway
topic MicroRNAs. Staining and Labeling. Myocardial Infarctation. Reperfusion. Tumor Necrosis Factor-alpha. Down-Regulation. Rats
Sprague-Dawley
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-76382021005008205&tlng=en
work_keys_str_mv AT weijunxu microrna124aprotectsthemyocardiumagainstischemiareperfusioninjurythroughregulationofthenotchsignalingpathway
AT shanjiang microrna124aprotectsthemyocardiumagainstischemiareperfusioninjurythroughregulationofthenotchsignalingpathway
AT qiliu microrna124aprotectsthemyocardiumagainstischemiareperfusioninjurythroughregulationofthenotchsignalingpathway