Background/Purpose: Promotional effects of resveratrol on myocardial mitochondrial energy metabolism in exercise-induced fatigue rats were investigated by network pharmacology and animal experiments. Method: In the present study, the effects of resveratrol on myocardial energy metabolism were assessed using network pharmacology with enrichment analysis. Forty-eight healthy male SD rats of 6–8 weeks of age were selected and randomly divided into blank control group (C), resveratrol administration group (R), exercise fatigue group (E), and exercise fatigue + resveratrol administration group (ER) with 12 rats in each group. Rats in E group and the exercise fatigue + ER group were weight-bearing 5% swimming for 60 min per day, exercising 6 days a week and 1 day off for 6 weeks. Results: 1,359 exercise-induced fatigue disease targets, 2,385 heart failure disease targets, and 266 resveratrol targets were screened; a total of 62 intersecting targets were identified. The GO-enriched pathway analysis showed that resveratrol treatment of exercise-induced fatigue rat heart failure mainly affected three aspects: Biological processes (circulatory system, regulatory system, and positive regulation of cell migration), cell synthesis (septal rafts, membrane microregion, and perinuclear region), and molecular functions (heme binding, tetrapyrrole binding, and protease activity); KEGG-enriched pathway analysis showed that resveratrol treatment of exercise-induced fatigue rat heart failure was mainly affected from cancer pathway, lipid and atherosclerosis pathway, and AMPK pathway. Compared with C, E rats showed a significant increase in heart weight and body weight (P < 0.05), a significant increase in the activity levels of CK-MB and cTnI (P < 0.01), significantly lower activity levels of myocardial COX and SDH (P < 0.01, P < 0.05), and significant decreases in the activity levels of the mitochondrial energy metabolism-related genes SIRT1, PGC-1Α, and ERRΑ with significantly lower mRNA expression levels (P < 0.01). Compared with E, ER rats showed a significant reduction in heart weight and body weight (P < 0.05), a significant reduction in the activity levels of CK-MB and cTnI (P < 0.05), a significant increase in the activity levels of myocardial COX and SDH (P < 0.01), and the mRNA of SIRT1, PGC-1Α, and ERRΑ expression levels were all significantly increased (P < 0.05). Conclusion/Discussion: Resveratrol ameliorated the extent of myocardial injury by improving myocardial energy metabolism in exercise-induced fatigue rats.
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