The dynamic changes and mechanism of no reflow injury after myocardial ischemia-reperfusion

ABSTRACT: This study aims to investigate the dynamic changes and correlation of no-reflow (NR) injury following myocardial ischemia and reperfusion, and to explore the underlying mechanism of NR injury through transcriptomic and metabolomic analysis. Methods: Healthy male SD rats were divided into two batches: fixed ischemia time and fixed reperfusion time. In the model group, the left anterior descending coronary artery was ligated and subsequently reperfused, while the Sham group, underwent threading without ligation. The myocardial area with NR and the ischemia area were assessed using thioflavin S and Evans blue staining, the cardiac function was measured by echocardiography, the myocardial enzyme activity was detected by automatic biochemical analyzer, and the mechanisms of NR phenomenon were analyzed via transcriptomic and metabolomic approaches, with validation through Western blot (WB) analysis. Results: The model group showed obvious NR phenomenon. During fixed reperfusion, NR and ischemia were the largest at 4 h of ischemia. In fixed ischemia, NR and ischemia area were the largest when reperfusion was performed for 24 hours. Compared with the Sham group, the myocardial enzyme activity of the rats in the vast majority of the model group was increased, and the cardiac function of the rats in all model groups was impaired. Metabolomics results showed that the main differential metabolites were citric acid and succinic acid, etc when NR occurred, and the main pathways there oxidative phosphorylation and TCA cycle. Transcriptome analysis showed that the expression levels of branched-chain aminotransferase 1 (Bcat1), 4-hydroxyphenylpyruvate dioxygenase (HPD) and glutathione transferase Zeta 1 (GSTZ1) were changed when NR occurred. The results of the enrichment of transcriptome biological functions involve tyrosine metabolism, etc., and are related to amino acid metabolites related to the TCA cycle. Metabolomics and transcriptomics results were analyzed using MetaboAnalyst 6.0 to show that when NR occurs, it affects energy metabolism and causes NR damage by regulating the TCA cycle, which is mainly related to the metabolism of amino acids such as tyrosine. WB results showed that the protein expression of Bcat1, HPD and GSTZ1 decreased after NR injury.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS15452 | MetaboLights | 2026-08-25

REPOSITORIES: MetaboLights