Protective effects of exogenous sodium hydrosulfide on the structure and function of myocardial mitochondria of mice with sepsis

Objective: This study aimed to investigate the protective effects of exogenous sodium hydrosulfide (NaHS) on the structure and function of myocardial mitochondria and the survival rate of mice with sepsis and the potential mechanism. Methods: 70 male C57BL/6 mice were randomly assigned into 7 groups: normal control group, sham group, sepsis group, sepsis + 25 μmol/L NaHS group, sepsis + 50 μmol/L NaHS group, sepsis + 100 μmol/L NaHS group and sepsis + 200 μmol/L NaHS group. Sepsis was induced by cecal ligation and perforation (CLP). NaHS was intraperitoneally injected. At 12 h after surgery, mice were sacrificed and the heart was harvested for the detection of microstructure, the contents of ATP, ROS, MDA and GSH, and mRNA expression of PGC-1α and Nrf2 mRNA. Another 50 mice were randomly divided into 5 groups: sepsis group, sepsis + 25 μmol/L NaHS group, sepsis + 50 μmol/L NaHS group, sepsis + 100 μmol/L NaHS group, and sepsis + 200 μmol/L NaHS group. Results: In sepsis group, the structure of myocardial mitochondria was significantly damaged, ATP reduced, ROS, and MDA increased, GSH reduced, and mRNA expression of PGC-1α and Nrf2 increased. When compared with sepsis group, the mitochondrial structure was improved, ATP increased, ROS and MDA reduced, GSH increased, and mRNA expression of PGC-1α and Nrf2 further increased after NaHS treatment, but these changes were NaHS concentration dependent. PGC-1α mRNA expression was positively related to Nrf2 mRNA. MDA content was negatively associated with PGC-1α and Nrf2 mRNA expression. ATP and GSH contents were positively related to PGC-1α and Nrf2 mRNA expression. The 48 hours survival rate after modeling of mice in NaHS intervention group was higher than that in CLP group, and which was the highest in 100 μmol/L group. Conclusion: Exogenous NaHS is able to increase myocardial GSH content and PGC-1α and Nrf2 mRNA expression to combat with oxidative stress in sepsis, which is helpful for the improvement of myocardial mitochondrial structure and function and the survival rate of sepsis mice. 100 μmol/L is the optimum experimental concentration in this study.