Suppressing receptor-interacting protein 140: a new sight for esculetin to treat myocardial ischemia/reperfusion injury

Abstract

The purpose of the present study was to evaluate the cardioprotective effect of esculetin (ES) on myocardial ischemia/reperfusion (I/R) damage in rats and investigate the potential mechanism. Rats were randomly assigned to 4 groups, namely, sham group, I/R group, I/R + ES (20 mg kg⁻¹, intragastric administration, 7 days) group, and I/R + ES (40 mg kg⁻¹, intragastric administration, 7 days) group. The indices of myocardial injury, inflammatory cytokines and apoptosis-related parameters were detected. ST segment elevation of electrocardiograph (ECG) was observed in ischemia rats. The results demonstrated that ES administration effectively decreased the levels of creatinine kinase (CK), lactate dehydrogenase (LDH), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) in serum and reduced the myocardial infarction area compared with the I/R group. ES treatment also markedly restored the activity of superoxide dismutase (SOD) and decreased the amount of malondialdehyde (MDA) of the I/R rats. Moreover, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay suggested that ES treatment suppressed myocardial cell apoptosis, which might be associated with the up-regulation of Bcl-2 and the down-regulation of Bax, caspase-3 and caspase-9. In addition, ES attenuated myocardial I/R induced injury in rats by inhibiting the receptor-interacting protein 140 (RIP140)/nuclear factor kappa B (NF-κB) inflammatory pathway. Collectively, it could be assumed that ES significantly improved myocardial I/R injury in rats partially through suppression of myocardial apoptosis and inflammation mediated by the RIP140/NF-κB pathway.