Abstract
Objective To explore the oxidative stress and inflammatory mechanisms of resveratrol intervention in myocardial ischemia-reperfusion injury (MIRI). Methods The potential targets of resveratrol were predicted by PharmMapper. The MIRI genes were collected by Online Mendelian Inheritance in Man (OMIM), GeneCards is used to collect related disease genes, and String is used for enrichment analysis. Animal experiments were then performed to verify the systematic pharmacological results. Hematoxylin-eosin (HE) staining was used to observe myocardial damage. The levels of serum interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in each experimental group were detected. The protein and mRNA expressions of Toll-like receptor 4 (TLR4), nuclear factor-kappa (NF-κB) p65, IL-1β, IL-6, and TNF-α in rat myocardial tissue were measured. Results The results of systematic pharmacology showed that insulin resistance, FoxO signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, PI3K-Akt signaling pathway, ErbB signaling pathway, T-cell receptor signaling pathway, peroxisome proliferator-activated receptors (PPAR) signaling pathway, Ras signaling pathway, TNF signaling pathway, and so on were regulated to improve MIRI. The results of animal experiments showed that the myocardial cells of the sham operation group were arranged in fibrous form, and the myocardial ischemia-reperfusion injury group had obvious cell morphology disorder. Compared with the MIRI group, the resveratrol group had a certain degree of relief. Compared with the MIRI group, serum IL-1β, TNF-α, and IL-6 in the resveratrol group was significantly reduced (P < 0.05), and myocardial tissue TLR4, NF-κB p65, IL-1β, IL-6, and TNF-α mRNA and protein expressions were significantly reduced (P < 0.05). Conclusion Resveratrol can effectively improve MIRI, and its mechanism may be related to antioxidative stress and anti-inflammatory.
Highlights
Coronary artery disease (CAD) refers to heart disease caused by coronary artery atherosclerosis that causes lumen stenosis or occlusion, leading to myocardial ischemia, hypoxia, or necrosis, known as ischemic heart disease [1]
Evidence-Based Complementary and Alternative Medicine myocardial ischemia-reperfusion injury (MIRI) [7, 8]. e factors leading to MIRI damage include inflammation, oxidative stress, calcium overload, mitochondrial permeability transition pore opening, and energy metabolism disorders [9,10,11]. e intervention of these pathological processes that lead to MIRI damage is a potential strategy to prevent cardiomyocyte death during MIRI [12, 13]
Animal Modeling Methods. e rats were fasted for 12 hours before the operation, and the rats were anesthetized by intraperitoneal injection of 3% pentobarbital sodium 30 mg/ kg. e rat was fixed on the operating table in the supine position and connected to the BL-420 biological function system, electrocardiograph (ECG) standard II lead, tracheal intubation, and ventilator-assisted breathing were recorded, the third and fourth ribs on the left side of the sternum were incised, and the pericardium was separated. en the left anterior descending coronary artery (LAD) was ligated with 6.0 silk thread, and both ends of the thread were threaded into the PE tube, and the polyethylene (PE) tube was clamped with a needle holder and pushed forward to cause cardiac compression ischemia
Summary
Coronary artery disease (CAD) refers to heart disease caused by coronary artery atherosclerosis that causes lumen stenosis or occlusion, leading to myocardial ischemia, hypoxia, or necrosis, known as ischemic heart disease [1]. E factors leading to MIRI damage include inflammation, oxidative stress, calcium overload, mitochondrial permeability transition pore (mPTP) opening, and energy metabolism disorders [9,10,11]. E intervention of these pathological processes that lead to MIRI damage is a potential strategy to prevent cardiomyocyte death during MIRI [12, 13]. E biological activity of resveratrol has antioxidative stress, antiinflammatory, heart protection, immune regulation, antidiabetic, antiaging, and anticancer properties [17,18,19], especially playing an important role in the protection of myocardial damage [20, 21]. Its molecular mechanism is not fully understood; especially, the biological network of resveratrol in regulating MIRI is still unknown
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