RESUMO
Ischemia/reperfusion (I/R) injury is a serious clinical condition characterized by high morbidity and mortality rates. Donepezil plays a neuroprotective role in I/Rassociated diseases. The aim of the present study was to investigate the role and the potential mechanism of action of donepezil in I/Rinduced myocardial microvascular endothelial cell dysfunction. An I/R model was simulated using oxygenglucose deprivation/reoxygenation (OGD/R) injury in human cardiac microvascular endothelial cells (CMECs). Cell viability and lactate dehydrogenase release were examined following treatment with donepezil. Commercial kits were used to evaluate cell apoptosis, cell permeability and caspase3 activity. The expression levels of apoptosisassociated proteins, as well as proteins found in tight junctions or involved in the poly(ADPribose) polymerase 1 (PARP1)/NFκB pathway, were measured using western blotting. These parameters were also examined following PARP1 overexpression. The results demonstrated that donepezil increased cell viability and reduced toxicity in OGD/Rtreated CMECs. The apoptotic rate, caspase3 activity and protein expression levels of Bax and cleaved caspase3 were significantly reduced following donepezil treatment, which was accompanied by Bcl2 upregulation. Moreover, cell permeability was notably reduced, coupled with a marked increase in the expression of tight junctionassociated proteins. The expression levels of proteins related to PARP1/NFκB signaling were significantly downregulated in CMECs following donepezil treatment. However, the protective effects of donepezil on OGD/Rinduced CMEC injury were reversed following PARP1 overexpression. In conclusion, donepezil suppressed OGD/Rinduced CMEC dysfunction via PARP1/NFκB signaling. This finding provided insight into the mechanism underlying myocardial I/R injury.