[Animal modeling] - Explore 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 in vivo based on the screening method of network pharmacological information.

  Methods TCMSP database was used to screen RSV target genes, and GeneCards database was used to screen MI/R injury 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. The gene network was drawn through the Cytoscape software, and the core target genes were screened; Finally, we use R language software to analyze the GO and KEGG pathways of these target genes. Thirty SD rats were randomly divided into sham operation group (Sham), ischemia reperfusion group (MI/R) and resveratrol administration group (RSV). The rat model of MI/R injury was induced by ligating the anterior descending branch of the left coronary artery, and then the contents of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (cTn I) and myocardial infarct area in the plasma of the rats were measured. Myocardial structure was observed by HE staining, cardiomyocyte apoptosis was detected by TUNEL staining, and apoptosis related proteins caspase-3, Bcl-2 and tumor necrosis factor related apoptosis inducing ligand (TRAIL) were detected by immunohistochemistry and Western blot.

  Results there were 86 core target genes for RSV treatment of MI / R injury through online pharmacological information screening, mainly involving biological processes such as cytokine receptor, phosphatase binding and death receptor, as well as AGE-RAGE signal pathway and apoptosis signal pathway involved in regulating diabetes complications. In vivo experimental results in rats showed that compared with Sham group, the expression level of TRAlIL protein in myocardial tissue of MI/R group was significantly higher (P<0.01), the content of LDH, CK and cTn Ⅰ in plasma was significantly increased (P<0.01), the area of myocardial infarction was increased, and the arrangement of muscle fibers in myocardial tissue was disordered, the apoptosis rate and the expression level of caspase-3 protein were significantly increased (P<0.05), and the expression of Bd-2 was significantly decreased (P<0.05); In RSV group, the arrangement of myocardial fibers was relatively regular, the content of LDH, CK, cTnI and the expression of TRAIL protein decreased, the area of myocardial infarction decreased, and the rate of apoptosis decreased (all P<0.05).

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