To investigate the role of the phosphatidyqinositol-3 kinase / protein kinase B / nuclear factor-erythroid 2 related factor 2 (PI3K/Akt/Nrf2) pathway in remifentanil postconditioning-induced protection against myocardial ischemia-reperfusion (IR) injury in rats.

Establishing a rat model of myocardial ischemia-reperfusion injury (MIRI) by left anterior descending coronary artery ligation. Subsequently, the rats were randomly assigned to the following groups: control (only threading was performed without ligation), model (ischemia was induced for 30 minutes followed by 30 minutes of reperfusion), experimental (remifentanil was continuously infused by at a dose of 10 μg·kg^-1·min^-1 from 25 minutes of ischemia to 5 minutes before reperfusion), LY294002 (while receiving remifentanil intervention, 0.3 mg·kg^-1 LY294002 was administered), and ML385 (while receiving remifentanil intervention, 30 mg·kg^-1 ML385 was administered). Serum levels of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). Apoptosis index (AI) of myocardial cells in each group was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) were measured using real-time quantitative polymerase chain reaction.

The measured parameters for the control, model, experimental, LY294002, and ML385 groups were as follows. Serum interleukin-6 (IL-6) were 0.76±0.15, 3.44±0.35, 1.46±0.37, 3.17±0.28 and 3.07±0.18. IL-1β were 0.34±0.08, 1.18±0.21, 0.66±0.28, 0.94±0.13 and 0.81±0.25, respectively. Serum tumor necrosis factor-α (TNF-α) were 0.98±0.17, 2.38±0.27, 1.17±0.21, 2.27±0.26 and 2.66±0.16, respectively. Apoptosis index (AI) were 0.95±0.67, 20.73±1.63, 10.20±2.48, 15.69±2.41 and 16.31±1.55, respectively. PI3K mRNA relative expression level were 1.00±0.08, 1.69±0.15, 1.90±0.12, 0.98±0.14 and 1.78±0.13, respectively. Akt mRNA relative expression level were 1.00±0.09, 1.56±0.22, 1.85±0.13, 0.87±0.21 and 1.69±0.31, respectively. Nrf2 mRNA relative expression level were 1.00±0.08, 2.62±0.16, 3.11±0.28, 1.37±0.25 and 1.03±0.14, respectively. Statistically significant differences were observed for all the above parameters when comparing the experimental group with the model group, and when comparing the LY294002 and ML385 groups with the experimental group (P<0.05, P<0.01, P<0.001, P<0.0001).

Remifentanil postconditioning exerts a protective effect on myocardial IR injury by reducing IR-induced cardiomyocyte apoptosis and inflammatory response in rats, and may be related to the PI3K / Akt / Nrf2 signaling pathway.