Dataset Information

Exploring the Mechanism of Edaravone for Oxidative Stress in Rats with Cerebral Infarction Based on Quantitative Proteomics Technology.

ABSTRACT:

Objective

To explore the mechanism of edaravone in the treatment of oxidative stress in rats with cerebral infarction based on quantitative proteomics technology.

Method

The modified Zea Longa intracavitary suture blocking method was utilized to make rat CI model. After modeling, the rat was intragastrically given edaravone for 7 days, once a day. After the 7-day intervention, the total proteins of serum were extracted. After proteomics analysis, the differentially expressed proteins are analyzed by bioinformatics. Then chemoinformatics methods were used to explore the biomolecular network of edaravone intervention in CI.

Result

The neurological scores and pathological changes of rats were improved after the intervention of edaravone. Proteomics analysis showed that in the model/sham operation group, 90 proteins in comparison group were upregulated, and 26 proteins were downregulated. In the edaravone/model group, 21 proteins were upregulated, and 41 proteins were downregulated. Bioinformatics analysis and chemoinformatics analysis also show that edaravone is related to platelet activation and aggregation, oxidative stress, intercellular adhesion, glycolysis and gluconeogenesis, iron metabolism, hypoxia, inflammatory chemokines, their mediated signal transduction, and so on.

Conclusion

The therapeutic mechanism of edaravone in the treatment of CI may involve platelet activation and aggregation, oxidative stress, intercellular adhesion, glycolysis and gluconeogenesis, iron metabolism, hypoxia, and so on. This study revealed the serum protein profile of edaravone in the treatment of cerebral infarction rats through serum TMT proteomics and discovered the relevant mechanism of edaravone regulating iron metabolism in cerebral infarction, which provides new ideas for the study of edaravone intervention in cerebral infarction and also provides reference information for future research on the mechanism of edaravone intervention in iron metabolism-related diseases.

SUBMITTER: Wang G

PROVIDER: S-EPMC8752268 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundShuxuening injection (SXN) is a traditional Chinese medicine used in the treatment of cardiovascular diseases. Whether it can provide better outcomes when combined with edaravone injection (ERI) for the treatment of acute cerebral infarction is not well determined. Therefore, we evaluated the efficacy of ERI combined with SXN versus that of ERI alone in patients with acute cerebral infarction.MethodsPubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang electronic databases were searched up to July 2022. Randomized controlled trials comparing the outcomes of efficacy rate, neurologic impairment, inflammatory factors, and hemorheology were included. Odds ratio or standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to present the overall estimates. The quality of the included trials was evaluated by the Cochrane risk of bias tool. The study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses.ResultsSeventeen randomized controlled trials were included consisting of 1607 patients. Compared to ERI alone, treatment with ERI plus SXN had a greater effective rate than ER alone (odds ratio = 3.94; 95% CI: 2.85, 5.44; I2 = 0%, P < .00001), a lower National Institute of Health Stroke Scale (SMD= -1.39; 95% CI: -1.73, -1.05; I2 = 71%, P < .00001), lower neural function defect score (SMD= -0.75; 95% CI: -1.06,-0.43; I2 = 67%, P < .00001), and lower level of neuron-specific enolase (SMD= -2.10; 95% CI: -2.85, -1.35; I2 = 85%, P < .00001). ERI plus SXN treatment provided significant improvements in whole blood high shear viscosity (SMD = -0.87; 95% CI: -1.17, -0.57; I2 = 0%, P < .00001), and whole blood low shear viscosity (SMD = -1.50; 95% CI: -1.65, -1.36; I2 = 0%, P < .00001) compared to ERI alone.ConclusionERI plus SXN showed better efficacy than ERI alone for patients with acute cerebral infarction. Our study provides evidence supporting the application of ERI plus SXN for acute cerebral infarction.