To investigate the effect of resveratrol on the nuclear factor-E2 related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway in myocardial ischemia-reperfusion (I/R) injury of type 2 diabetes mellitus rats.

Sixty Sprague-Dawley rats with type 2 diabetes mellitus were randomly divided into a sham operation group, a I/R group, a resveratrol preconditioning (R) group, and a resveratrol preconditioning + EX527 (RE) group, 15 rats in each group. Myocardial I/R injury was produced by ligating the left coronary anterior descending artery for 30 min followed by 120 min reperfusion. Rats in the R group and RE group were intraperitoneally injected with resveratrol (15 mg/kg, once a day) for 7 days before the operation; rats in the sham operation group and I/R group were intraperitoneally injected with the equal capacity of isotonic NaCl solution; rats in the RE group also received EX527 (1 μg/kg) by caudal vein injection at 15 min before ischemia. At the end of 120 min reperfusion, blood samples were taken for detecting the concentration of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) by the enzyme-linked immunosorbent assay. Then rats were sacrificed in each group; the pathological changes of myocardium were observed by hematoxylin-eosin (HE) staining and the myocardial infarct size was measured by 2,3,5-triphenyltetrazolium chloride. The levels of malondialdehyde and superoxide dismutase (SOD) were compared among the four groups. The expression levels of myocardial silent information regulator of transcription 1 (SIRT1), Nrf2, and HO-1 protein were detected using Western-blotting.

From HE staining, the myocardial cells were slightly broken and edematous, with a small amount of inflammatory cells in the sham operation group; the myocardial fibers were disorderly arranged, with myocardial interstitial congestion and edema infiltrated by a large number of inflammatory cells in the I/R group; the myocardial tissue was relatively structurally neat, with occasional karyopyknosis in the R group; the myocardial fibers were arranged in a disorderly way, with obvious karyopyknosis and inflammatory cells in the RE group. No myocardial infarction occurred in the sham operation group. The myocardial infarct size in the I/R group, R group, and RE group showed significant differences [(51 ± 6)%, (37 ± 4)%, (41 ± 3)%; F = 160.703, P < 0.001]. It was much smaller in the R group and RE group than in the I/R group, and was smallest in the R group (all P < 0.05). The levels of LDH, CK-MB, malondialdehyde, SOD, SIRT1, Nrf2, and HO-1 all showed significant differences among the four groups (F = 144.101, 158.545, 53.682, 99.273, 50.121, 59.153, 143.702; all P < 0.001). Compared with the sham operation group, the levels of LDH, CK-MB, and malondialdehyde increased obviously in the I/R group, R group and RE group, and the levels of SOD, SIRT1, Nrf2, and HO-1 decreased (all P < 0.05). Compared with the I/R group, the levels of LDH, CK-MB, and malondialdehyde decreased obviously in the R group and RE group, which decreased most in the R group, and the levels of SOD, SIRT1, Nrf2, and HO-1 increased, which increased most in the R group (all P < 0.05).

Resveratrol can alleviate oxidative stress and myocardial I/R injury in type 2 diabetes mellitus rats by promoting SIRT1 to activate the Nrf2/HO-1 signaling pathway.