To explore the mechanism of prasugrel (PRAS) in alleviating oxidative stress of myocardial ischemia reperfusion (IR) by inducing pyroptosis of rat cardiomyocytes based on nuclear factor erythroid derived 2-like 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway.

SD rats were randomly divided into sham operation group (only the heart was exposed, no IR model was constructed, and the same amount of normal saline was injected into the stomach), model group (IR rat model was constructed, and the stomach was given an equal amount of 0.9% NaCl), the experimental-L group (model group rats were intragastric with 5 mg·kg^-1 PRAS), the experimental-M group (model group rats were intragastric with 10 mg·kg^-1 PRAS), and experimental-H group (model group rats were intragastric with 15 mg·kg^-1 PRAS). The serum levels of myocardial injury markers and oxidative stress factors were detected by enzyme-linked immunosorbent assay. The relative expression levels of pyroptosis-related proteins and Nrf2/HO-1/NQO1 signaling pathway-related proteins in myocardial tissue were detected by Western blot.

The contents of cardiac troponin Ⅰ (cTnⅠ) in sham operation group, model group, experimental-L group, experimental-M group and experimental-H group were (264.52±39.04), (558.40±101.68), (477.65±64.33), (429.71±75.94) and (313.84±52.26) pg·mL^-1, respectively; the creatine kinase isoenzyme (CK-MB) levels were (0.68±0.11), (2.76±0.45), (1.92±0.27), (1.53±0.23) and (1.11±0.19) U·L^-1, respectively; the levels of malondialdehyde (MDA) were (4.05±0.68), (10.12±1.74), (8.44±1.26), (6.79±1.05) and (5.47±1.02) nmol·L^-1, respectively; the relative expression levels of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) were 1.00±0.14, 2.16±0.32, 1.72±0.25, 1.54±0.28 and 1.28±0.21, respectively; the relative expression levels of Nrf2 were 1.00±0.15, 0.32±0.04, 0.39±0.05, 0.61±0.10 and 0.80±0.13, respectively. The above indexes of model group were compared with those of sham-operation group, and those of experimental-L, experimental-M and experimental-H groups were compared with those of model group (P<0.05, P<0.01, P<0.001).

PRAS may resist oxidative stress and reduce pyroptosis and apoptosis of myocardial cells by activating Nrf2/HO-1/NQO1 signaling pathway, thereby alleviating IR injury and protecting cardiac function.