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

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-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta); 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.

Automated summary

This study investigated the protective effect of edaravone (ED) on hepatic ischemia-reperfusion injury (HIRI) in rats and explored its mechanism involving exosomal miRNA. The results showed that ED could attenuate the liver damage caused by HIRI, as evidenced by lower levels of ALT, AST, oxidative stress, and inflammatory markers. Additionally, ED prevented the downregulation of miRNA PC-3p-190-42101 and its expression was correlated with the level of inflammatory factors. These findings suggest that ED protects the liver from IRI by regulating the inflammatory factors through the modulation of miRNA expression in plasma exosomes.