Fig. 1

Schematic illustration of the present study. a Pretreatment experiment. Melatonin or Compound C was dissolved in DMSO and given to mice every 2 days for 6 days before CLP injury. Mice were randomly allocated into the following groups: (1) mice injected with 1 ml/kg DMSO and subjected to sham surgery; (2) mice injected with 1 ml/kg DMSO and then subjected to CLP surgery; (3) mice treated with melatonin and then subjected to CLP surgery. In the third group, different concentrations of melatonin (15 mg/kg, 30 mg/kg, or 60 mg/kg) were administered to mice to observe the effect of MEL on survival rate within 72 h, among which 30 mg/kg was selected for further analysis, including cardiac function, biochemistry, and molecular parameters. For Compound C (CC) experiment, two groups were added: (4) mice injected with 30 mg/kg melatonin and 2.5 mg/kg CC and then subjected to CLP surgery; (5) mice injected with 2.5 mg/kg CC and then subjected to CLP surgery. b Posttreatment experiment. Melatonin was dissolved in DMSO and given to mice at 30 min and 4 h post CLP. Mice were randomly allocated into the following groups: (1) mice subjected to sham surgery and then injected with 1 ml/kg DMSO; (2) mice subjected to CLP surgery and then injected with 1 mg/kg DMSO; (3) mice subjected to CLP surgery and treated with 30 mg/kg melatonin. c Combination therapy. Melatonin, azithromycin, or vancomycin were dissolved in DMSO and given to mice at 30 min and 4 h post CLP. Mice were randomly allocated into the following groups: (1) mice subjected to CLP surgery and then treated with 10 mg/kg azithromycin (or vancomycin); (2) mice subjected to CLP surgery and then treated with 10 mg/kg (or vancomycin) and 30 mg/kg melatonin