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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

Effect of Edaravone on MicroRNA Expression in Exosomes after Hepatic Ischemia-reperfusion Injury

Author(s): Yanxia Fei, Jiali Shao, Ge Huang, Lijuan Wang, Shuangfa Zou, Huiping Sun, Chumei Zheng and Jinfeng Yang*

Volume 15, Issue 6, 2022

Published on: 26 January, 2022

Article ID: e301121198440 Pages: 13

DOI: 10.2174/1874467214666211130162152

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Abstract

Background and Objective: Hepatic ischemia-reperfusion injury (HIRI) results in serious complications after liver resection and transplantation. Edaravone (ED) has a protective effect on IRI. This study was designed to evaluate whether ED could protect the liver of rats from HIRI injury and explored its exosomal miRNA-related mechanism.

Methods: The sham group, hepatic ischemia/reperfusion (IR group), and hepatic ischemia/reperfusion + edaravone (ED group) models were established. We determined the protective effect of ED by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD); enzyme-linked immunosorbent assay for tumor necrosis factor- α (TNF-α) and interleukin-1β (IL-1β); hematoxylin-eosin staining and immunohistochemistry for histopathological changes. Exosomal miRNAs were subjected to second-generation sequencing to identify their differential expression. The results were analyzed using bioinformatics methods and validated using real-time quantitative polymerase chain reaction (RT-qPCR).

Results: HIRI rats showed higher levels of ALT, AST, oxidative stress, and inflammatory markers; ED attenuated these effects. The sequencing results showed 6 upregulated and 13 downregulated miRNAs in the IR vs. sham groups, 10 upregulated and 10 downregulated miRNAs in the ED vs. IR groups. PC-3p-190-42101 was screened as an overlapping differentially expressed miRNA, and RT-qPCR validation showed that its expression in HIRI rats was significantly decreased; ED prevented this downregulation. Moreover, the expression of PC-3P-190-42101 was significantly correlated with the level of inflammatory factors.

Conclusion: These findings indicate that ED can regulate the level of inflammatory factors by affecting the expression of miRNA PC-3p-190-42101 in plasma exosomes to protect the liver from IRI.

Keywords: Hepatic ischemia-reperfusion injury, edaravone, oxidative stress, inflammatory, exosomes, microRNAs.

Graphical Abstract

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