Abstract: Objective To investigate the protective effect of resveratrol (RSV) against myocardial ischemia-reperfusion (MI/R) injury and its mechanism in rats based on the network pharmacological information screening method. Methods TCMSP database was used to screen the target genes of RSV, and GeneCards database was used to screen MI/R injury-related target genes. R programming language was used to achieve the intersection of the two sets, indicating the possible target genes for RSV treating MI/R injury, then a gene network was drawn by Cytoscape software to screen out the core target genes. Finally, the GO function and KEGG pathway of the screened gene targets were analyzed by R language. Thirty SD rate were randomly divided into a sham operation group (Sham group), an ischemia-reperfusion group (MI/R group) and a RSV administration group (RSV group). The MI/R injury rat model was induced by ligating the anterior descending coronary artery. The serum contents of lactate dehydrogenase (LDH), creatine kinase (CK) and cardiac troponin Ⅰ (cTn Ⅰ) as well as the size of myocardial infarction area in the MI/R injuny model rats induced by ligature of left anterior descending of coronary artery were determined. Hematoxylin-eosin staining (HE) was used to observe the structure of myocardium, TUNEL staining was used to detect cardiomyocyte apoptosis, immunohistochemistry and Western blotting were used to detect the expressions of apoptosis-related proteins (caspase-3 and Bcl-2) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Results According to the screening of pharmacology information, there were 86 core genes in RSV treatment of MI/R injury, which mainly involved the biological processes such as cytokine receptors, phosphatase binding, and death receptors, as well as the AGE-RAGE signaling pathway, apoptosis and other signaling pathways regulating diabetic complications. Compared with the Sham group, the expression of TRAIL protein, the contents of LDH, CK and cTn Ⅰ, and the infarct size increased (P<0.01, or P<0.05), while the arrangement of myocardial muscle fibers was disordered, and the apoptosis rate and caspase-3 protein expression level increased (P<0.05), but the expression of Bcl-2 was down-regulated (P<0.05). However, in the RSV group, the arrangement of myocardial muscle fibers was relatively regular, while the expression of TRAIL protein, the contens of LDH, CK and cTn Ⅰ, as well as the infarct size and apoptosis rate were significantly reduced (all P<0.05). Conclusion RSV may inhibit apoptosis and reverse MI/R injury by regulating TRAIL protein experssion.

Key words: Network pharmacology, Resveratrol, Myocardial ischemia-reperfusion, Tumor necrosis factor-related apoptosis-inducing ligand, Apoptosis, Rats