【Animal Modeling】-Exploring the molecular mechanism of resveratrol against myocardial ischemia-reperfusion injury in rats based on network pharmacology

  Objective To explore the effect of resveratrol on myocardial ischemia-reperfusion injury in rats and its mechanism of action in rats based on the network pharmacology information screening method.

  Methods The TCMSP database was used to screen the gene targets of RSV, and the GeneCards database was used to screen the MI/R damage-related target genes. The R language software was used to intersect RSV and MI/R-related target genes, and the possible target genes for RSV treatment of MI/R injury were screened, and the gene network was drawn by Cytoscape software to screen out the core target genes; Target genes were analyzed by GO and KEGG pathways. Thirty SD rats were randomly divided into sham-operated group (Sham), ischemia-reperfusion group (MI/R) and resveratrol-administered group (RSV). The MI/R injury rat model was induced by ligation of the left anterior descending coronary artery, and then the plasma levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I ( cardiac troponin I, cTn I) content and myocardial infarction size. HE staining was used to observe myocardial structure, TUNEL staining was used to detect myocardial cell apoptosis, and immunohistochemistry and Western blotting were used to detect apoptosis-related proteins caspase-3, Bcl-2 and tumor necrosis factor-related apoptosis-inducing ligands in myocardial tissue. -related apoptosis-inducing ligand, TRAIL) expression.

  Results The network pharmacology information screening found that there were 86 core target genes of RSV in the treatment of MI/R injury, mainly involving biological processes such as cytokine receptors, phosphatase binding and death receptors, as well as AGE-RAGE involved in the regulation of diabetic complications. signaling pathway and apoptosis signaling pathway. The results of in vivo experiments in rats showed that compared with the Sham group, the expression level of TRAlIL protein in the myocardial tissue of the MI/R group was significantly increased (P<0.01), and the levels of LDH, CK and cTn I in the plasma were significantly increased (all P<0.01). The myocardial infarction area increased, the arrangement of muscle fibers in myocardial tissue was disordered, the apoptosis rate and the expression of caspase-3 protein were significantly increased (P<005), and the expression of Bd-2 was significantly down-regulated (P<0.05). The arrangement of muscle fibers was relatively regular, the contents of LDH, CK, cTn I and TRAIL protein were decreased, the myocardial infarction area was decreased, and the apoptosis rate was decreased (all P<0.05).

  Conclusion RSV may inhibit cell apoptosis by regulating the expression of TRA1IL protein, thereby reversing MI/R injury.