Mechanisms of sufentanil on alleviating sepsis-induced myocardial injury through activating AMPK/Nrf2/HO-1 pathways,mediating oxidative stress and inhibiting ferroptosis
10.11816/cn.ni.2025-241823
- VernacularTitle:舒芬太尼激活AMPK/Nrf2/HO-1通路介导氧化应激及铁死亡减轻脓毒症心肌损伤的机制
- Author:
Xuan XIANG
1
;
Wen MENG
;
Junjin CHEN
;
Fanghong CHEN
;
Haiying LI
;
Xueming HE
Author Information
1. 徐州医科大学研究生院,江苏徐州 221004;徐州医科大学附属连云港市立东方医院心血管内科,江苏连云港 222042
- Publication Type:Journal Article
- Keywords:
Sufentanil;
AMPK/Nrf2/HO-1 pathway;
Oxidative stress;
Ferroptosis;
Sepsis-induced myocardial in-jury
- From:
Chinese Journal of Nosocomiology
2025;35(10):1460-1465
- CountryChina
- Language:Chinese
-
Abstract:
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 estab-lished 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 respec-tively inoculated and incubated in culture media containing 25 mg/L of LPS,and the culture media were respec-tively 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 cul-ture 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 gluta-thione peroxidase(GSH-Px)were detected.The Fe2+level of the cells was detected by iron ion colorimetric meth-od.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 succes-sively 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 mecha-nism may be associated with activation of AMPK/Nrf2/HO-1 signaling pathways,inhibition of ferroptosis,oxi-dative stress injury and inflammatory reactions.
