Indobufen alleviates apoptosis by the PI3K/Akt/eNOS pathway in myocardial ischemia‒reperfusion (I/R) injury.

Indobufen is a potential antiplatelet drug; the aim of this study was to investigate the pharmacodynamic effects and potential mechanisms of indobufen in a myocardial ischemia/reperfusion (I/R) injury rat model, providing another effective option for the pharmacological prevention of myocardial infarction. In the in vivo model, rats were orally administered indobufen daily. On the fifth day, after 30 min of occlusion of the left anterior descending coronary artery, the rats were reperfused for 2 h. In the in vitro model, the drug was incubated with H9C2 cells for 24 h before the establishment of an oxygen-glucose deprivation/reperfusion (OGD/R) model. Then, the hearts of the rats were collected for TTC staining and myocardial histopathological examination. Creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels in rat plasma and cell supernatants were detected with the appropriate kits. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and apoptosis-related proteins were used to assess myocardial apoptosis. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of p-Akt/Akt and p-eNOS/eNOS. Our results suggest that indobufen ameliorates I/R injury by reducing infarct size, attenuating oxidative stress injury, and inhibiting cardiomyocyte apoptosis. In addition, indobufen increased the expression of p-Akt and p-eNOS in myocardial tissues and H9C2 cells, and LY294002, a specific inhibitor of the PI3K pathway, reversed these protective effects. In conclusion, indobufen reduced myocardial apoptosis and oxidative stress by the PI3K/Akt/eNOS pathway, thereby attenuating MI/R injury and improving cardiac function.