OBJECTIVE To study the mechanisms and effect of sufentanil (SUF) on protection of sepsis-induced myocardial injury.

METHODS The in vitro experimental models of sepsis-induced myocardial injury were established by using lipopolysaccharide (LPS). The myocardial H9C2 cells were divided into the Control group, the LPS group, the SUF-L group, the SUF-M group, the SUF-H group, the SUF-H-ComC group and the SUF-H-ML385 group; the LPS group, the SUF-L group, the SUF-M group, the SUF-H group, the SUF-H-ComC group and the SUF-H-ML385 group were the experimental groups. The cells from the experimental groups were respectively inoculated and incubated in culture media containing 25 mg/L of LPS, and the culture media were respectively added SUF with the terminal dose of 0, 5, 10, 20, 20 and 20 μmol/L; the culture media of the SUF-H-ComC was added ComC with the terminal dose of 10 μmol/L, and the culture media of the SUF-H-ML385 was added ML385 with the terminal dose of 5 μmol/L. The cells from the Control group were incubated in normal culture media. The same amount of culture media and CCK-8 reagent without containing myocardial H9C2 cells were assigned as the blank group. The cell viability was determined by CCK-8 method, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD)and glutathione peroxidase (GSH-Px) were detected. The Fe²⁺ level of the cells was detected by iron ion colorimetric method. The levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α(TNF-α)in supernatant fluid of the culture media were detected with the use of enzyme-linked immunosorbent assay. The expression levels of adenosine 5′-monophosphate-activated protein kinas (AMPK), phosphorylated-AMPK(p-AMPK), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by means of Western Blot.

RESULTS The cell viability of the LPS group was lower than that of the Control group; the levels of ROS, MDA, LDH, Fe²⁺, IL-1β, IL-6 and TNF-α of the LPS group were higher than those of the Control group; the levels of SOD and GSH-Px of the LPS group were lower than those of the Control group; the expression levels of p-AMPK/AMPK, Nrf2 and HO-1 proteins of the LPS group were lower than those of the Control group(P < 0.05). As compared with the LPS group, the cell viability of the SUF-L group, the SUF-M group and the SUF-H group was successively increased, the levels of ROS, MDA, LDH, Fe²⁺, IL-1β, IL-6 and TNF-α were successively reduced, the levels of SOD and GSH-Px were successively elevated, and the expression levels of p-AMPK/AMPK, Nrf2 and HO-1 proteins were successively increased(P < 0.05). AMPK pathway inhibitor and Nrf2 pathway inhibitor could reverse the viability of SUF-affecting LPS-induced myocardial H9C2 cells, levels of ROS, MDA, LDH, Fe²⁺, SOD, GSH-Px, IL-1β, IL-6 and TNF-α and downregulated the expression levels of p-AMPK/AMPK, Nrf2 and HO-1 proteins(P < 0.05).

CONCLUSION SUF can improve the sepsis-induced myocardial injury, and the mechanism may be associated with activation of AMPK/Nrf2/HO-1 signaling pathways, inhibition of ferroptosis, oxidative stress injury and inflammatory reactions.