H₂S attenuates sepsis-induced cardiac dysfunction via a PI3K/Akt-dependent mechanism

The heart is the most vulnerable target organ in sepsis, and it has been previously reported that hydrogen sulfide (H₂S) has a protective role in heart dysfunction caused by sepsis. Additionally, studies have demonstrated that the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has a protective function during sepsis. However, the potential association between H₂S and PI3K/Akt in sepsis-induced cardiac dysfunction is unclear. Therefore, the PI3K inhibitor LY294002 was used to investigate the role of PI3K/Akt signaling in the protective effects of H₂S during sepsis-induced myocardial injury. A rat sepsis model was established using cecal ligation and puncture (CLP) surgery. Sodium hydrosulfide, a H₂S donor, was administered intraperitoneally (8.9 µmol/kg), and serum myocardial enzyme levels, inflammatory cytokine levels, cardiac histology and cardiomyocyte apoptosis were assessed to determine the extent of myocardial damage. The results demonstrated that exogenous H₂S reduced serum myocardial enzyme levels, decreased the levels of the inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increased the level of anti-inflammatory IL-10 following CLP. Staining of histological sections demonstrated that myocardial damage and cardiomyocyte apoptosis were alleviated by the administration of exogenous H₂S. Western blot analysis was used to detect phosphorylated and total PI3K and Akt levels, as well as NF-κB, B-cell lymphoma-2, Bcl-2-associated X protein (Bax) and caspase levels, and the results demonstrated that H₂S significantly increased PI3K and Akt phosphorylation. This indicated that the PI3K/Akt signaling pathway was activated by H₂S. Additionally, H₂S reduced Bax and caspase expression, indicating that apoptosis was inhibited, and decreased NF-κB levels, indicating that inflammation was reduced. Furthermore, the PI3K inhibitor LY294002 eliminated the protective effects of H₂S. In conclusion, the results of the current study suggest that exogenous H₂S activates PI3K/Akt signaling to attenuate myocardial damage in sepsis.